195 results on '"Kurt Kletter"'
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2. Supplementary Table 2 from Evaluation of Diffusion-Weighted Magnetic Resonance Imaging for Follow-up and Treatment Response Assessment of Lymphoma: Results of an 18F-FDG-PET/CT–Controlled Prospective Study in 64 Patients
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Markus Raderer, Julius Lukas, Werner Dolak, Leonhard Müllauer, Philipp Ubl, Ingrid Simonitsch-Klupp, Ulrich Jaeger, Christian Sillaber, Thomas Knogler, Michael Weber, Edit Porpaczy, Cathrin Skrabs, Barbara Kiesewetter, Helmut Prosch, Kurt Kletter, Georgios Karanikas, and Marius E. Mayerhoefer more...
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Supplementary Table 2. True positive (TP), false negative (FN), false positive (FP), and true negative (TN) regions for DWI-MRI at follow-up, relative to 18F-FDG-PET/CT
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- 2023
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3. Supplementary Table 1 from Evaluation of Diffusion-Weighted MRI for Pretherapeutic Assessment and Staging of Lymphoma: Results of a Prospective Study in 140 Patients
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Markus Raderer, Julius Lukas, Philipp Ubl, Alexander Gaiger, Werner Dolak, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Ulrich Jaeger, Christian Sillaber, Martha Hoffmann, Dominik Berzaczy, Katja Pinker-Domenig, Michael Weber, Edit Porpaczy, Cathrin Skrabs, Barbara Kiesewetter, Helmut Prosch, Kurt Kletter, Georgios Karanikas, and Marius E. Mayerhoefer more...
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PDF file - 24KB, Region-based results for DWI-MRI in Group A (DLBCL, follicular lymphoma, Hodgkin lymphoma, nMZL, MCL, peripheral T-cell lymphoma, and ALCL), and DWIMRI, 18F-FDG-PET/CT, and CE-CT in Group B (MALT lymphoma, SLL/CLL): true-positive (TP), false-negative (FN), false-positive (FP), and true negative (TN) regions. more...
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- 2023
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4. Supplementary Figure 1 from Evaluation of Diffusion-Weighted MRI for Pretherapeutic Assessment and Staging of Lymphoma: Results of a Prospective Study in 140 Patients
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Markus Raderer, Julius Lukas, Philipp Ubl, Alexander Gaiger, Werner Dolak, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Ulrich Jaeger, Christian Sillaber, Martha Hoffmann, Dominik Berzaczy, Katja Pinker-Domenig, Michael Weber, Edit Porpaczy, Cathrin Skrabs, Barbara Kiesewetter, Helmut Prosch, Kurt Kletter, Georgios Karanikas, and Marius E. Mayerhoefer more...
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PDF file - 388KB, A 63 year-old male patient with a histologically verified MALT lymphoma of the stomach (light blue arrows) and the left parotid gland (light blue arrowheads). The parotid lesion shows only a very faint tracer uptake on 18F-FDG-PET and the fused color-coded PET/CT that was interpreted as physiological muscle uptake by one rater and as mild inflammation of the gland by the other rater. On CE-CT, where the lesion was missed by both raters, the left parotid gland appears only slightly larger than the right gland, and there are some uncharacteristic calcifications. However, no lesion can be delineated. On DWI and fused color-coded DWI-MRI, the lesion shows a very high, clearly abnormally high signal, indicative of strong diffusion restriction (high cellular density). The thickened gastric wall shows no abnormal tracer uptake on PET and PET/CT and is unspecific on CE-CT, whereas it shows an abnormally high signal on DWI and DWI-MRI, in good accordance with the histologically verified lymphoma. Note: the homogeneous high signal of the spleen on DWI(-MRI) is physiological. more...
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- 2023
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5. Data from Evaluation of Diffusion-Weighted MRI for Pretherapeutic Assessment and Staging of Lymphoma: Results of a Prospective Study in 140 Patients
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Markus Raderer, Julius Lukas, Philipp Ubl, Alexander Gaiger, Werner Dolak, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Ulrich Jaeger, Christian Sillaber, Martha Hoffmann, Dominik Berzaczy, Katja Pinker-Domenig, Michael Weber, Edit Porpaczy, Cathrin Skrabs, Barbara Kiesewetter, Helmut Prosch, Kurt Kletter, Georgios Karanikas, and Marius E. Mayerhoefer more...
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Purpose: To determine the value of diffusion-weighted MRI (DWI-MRI) for pretherapeutic imaging of fluorodeoxyglucose (FDG)-avid lymphoma and lymphoma with variable FDG avidity.Experimental Design: Treatment-naïve patients with lymphoma who were referred for whole-body staging were included in this prospective study. Group A included patients with FDG-avid lymphoma (e.g., Hodgkin, diffuse large B-cell, and follicular lymphoma), whereas Group B included patients with lymphoma of variable FDG avidity [e.g., extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)]. All patients underwent DWI-MRI and 18F-FDG- positron emission tomography/computed tomography (PET/CT). Region-based sensitivity and agreement with Ann Arbor staging, relative to the reference standard, were calculated for DWI-MRI, and, in Group B, also 18F-FDG-PET/CT and contrast-enhanced (CE-) CT.Results: In Group A (100 patients), DWI-MRI had a region-based sensitivity of 97%, and with regard to staging, agreed with the reference standard in 94 of 100 patients (κ, 0.92). In Group B (40 patients; 38 MALT lymphomas and 2 small lymphocytic lymphomas/chronic lymphocytic leukemias), DWI-MRI, 18F-FDG-PET/CT, and CE-CT had region-based sensitivities of 94.4%, 60.9%, and 70.7%, respectively. With regard to staging in Group B, DWI-MRI, 18F-FDG-PET/CT, and CE-CT agreed with the reference standard in 37 of 40, 26 of 40, and 24 of 40 patients, with κ values of 0.89, 0.52, and 0.43, respectively.Conclusions: In patients with FDG-avid lymphoma, DWI-MRI seems to be only slightly inferior to 18F-FDG-PET/CT with regard to pretherapeutic regional assessment and staging. In patients with lymphoma subtypes that show a variable FDG avidity (e.g., MALT lymphoma), DWI-MRI seems to be superior to both 18F-FDG-PET/CT and CE-CT. Clin Cancer Res; 20(11); 2984–93. ©2014 AACR. more...
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- 2023
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6. Supplementary Figure 2 from Evaluation of Diffusion-Weighted MRI for Pretherapeutic Assessment and Staging of Lymphoma: Results of a Prospective Study in 140 Patients
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Markus Raderer, Julius Lukas, Philipp Ubl, Alexander Gaiger, Werner Dolak, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Ulrich Jaeger, Christian Sillaber, Martha Hoffmann, Dominik Berzaczy, Katja Pinker-Domenig, Michael Weber, Edit Porpaczy, Cathrin Skrabs, Barbara Kiesewetter, Helmut Prosch, Kurt Kletter, Georgios Karanikas, and Marius E. Mayerhoefer more...
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PDF file - 455KB, A 56-year old male patient with histologically verified, infra-diaphragmatic SLL/CLL in the retroperitoneal/paraaortic lymph nodes (light blue arrows). These nodal lymphoma manifestations show a high signal (i.e., diffusion restriction) on DWI and the fused color-coded DWI-MRI images, and were thus rated as positive. On the other hand, they fail to show an elevated tracer uptake, relative to the surrounding tissues, on the 18F-FDG-PET and the fused color-coded PET/CT images, and were thus rated as negative. On CE-CT, the lymph nodes were rated as positive due to their abnormal long-axis diameter (>1.5 cm). more...
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- 2023
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7. Supplementary Table 2 from Evaluation of Diffusion-Weighted MRI for Pretherapeutic Assessment and Staging of Lymphoma: Results of a Prospective Study in 140 Patients
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Markus Raderer, Julius Lukas, Philipp Ubl, Alexander Gaiger, Werner Dolak, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Ulrich Jaeger, Christian Sillaber, Martha Hoffmann, Dominik Berzaczy, Katja Pinker-Domenig, Michael Weber, Edit Porpaczy, Cathrin Skrabs, Barbara Kiesewetter, Helmut Prosch, Kurt Kletter, Georgios Karanikas, and Marius E. Mayerhoefer more...
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PDF file - 16KB, Region-based sensitivities and specificities (and 95% confidence intervals) of DWI-MRI in patients with DLBCL, follicular lymphoma, and Hodgkin lymphoma.
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- 2023
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8. Supplementary Figure Legends from Evaluation of Diffusion-Weighted MRI for Pretherapeutic Assessment and Staging of Lymphoma: Results of a Prospective Study in 140 Patients
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Markus Raderer, Julius Lukas, Philipp Ubl, Alexander Gaiger, Werner Dolak, Ingrid Simonitsch-Klupp, Leonhard Müllauer, Ulrich Jaeger, Christian Sillaber, Martha Hoffmann, Dominik Berzaczy, Katja Pinker-Domenig, Michael Weber, Edit Porpaczy, Cathrin Skrabs, Barbara Kiesewetter, Helmut Prosch, Kurt Kletter, Georgios Karanikas, and Marius E. Mayerhoefer more...
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PDF file - 62KB
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- 2023
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9. Supplementary Table 1 from Evaluation of Diffusion-Weighted Magnetic Resonance Imaging for Follow-up and Treatment Response Assessment of Lymphoma: Results of an 18F-FDG-PET/CT–Controlled Prospective Study in 64 Patients
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Markus Raderer, Julius Lukas, Werner Dolak, Leonhard Müllauer, Philipp Ubl, Ingrid Simonitsch-Klupp, Ulrich Jaeger, Christian Sillaber, Thomas Knogler, Michael Weber, Edit Porpaczy, Cathrin Skrabs, Barbara Kiesewetter, Helmut Prosch, Kurt Kletter, Georgios Karanikas, and Marius E. Mayerhoefer more...
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Supplementary Table 1. Histologic data, therapy schemes, and follow-up (FU) results according to 18F-FDG-PET/CT
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- 2023
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10. Lateralization of the serotonin-1A receptor distribution in language areas revealed by PET.
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Martin Fink 0002, Wolfgang Wadsak, Markus Savli, Patrycja Stein, Ulrike Moser, Andreas Hahn 0001, Leonhard-Key Mien, Kurt Kletter, Markus Mitterhauser, Siegfried Kasper, and Rupert Lanzenberger
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- 2009
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11. Multimodal imaging of human early visual cortex by combining functional and molecular measurements with fMRI and PET.
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Florian Gerstl, Christian Windischberger, Markus Mitterhauser, Wolfgang Wadsak, Alexander Holik, Kurt Kletter, Ewald Moser, Siegfried Kasper, and Rupert Lanzenberger
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- 2008
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12. Evaluation of Diffusion-Weighted Magnetic Resonance Imaging for Follow-up and Treatment Response Assessment of Lymphoma: Results of an 18F-FDG-PET/CT–Controlled Prospective Study in 64 Patients
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Edit Porpaczy, Werner Dolak, Kurt Kletter, Georgios Karanikas, Christian Sillaber, Cathrin Skrabs, Ingrid Simonitsch-Klupp, Thomas Knogler, Philipp Ubl, Julius Lukas, Ulrich Jaeger, Helmut Prosch, Leonhard Müllauer, Marius E. Mayerhoefer, Michael Weber, Barbara Kiesewetter, and Markus Raderer more...
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Adult ,Male ,Cancer Research ,Treatment response ,Radiography ,Whole body imaging ,Fluorodeoxyglucose F18 ,hemic and lymphatic diseases ,medicine ,Humans ,Whole Body Imaging ,cardiovascular diseases ,Prospective cohort study ,Aged ,Aged, 80 and over ,medicine.diagnostic_test ,business.industry ,Lymphoma, Non-Hodgkin ,Cancer ,Middle Aged ,medicine.disease ,Hodgkin Disease ,Lymphoma ,Diffusion Magnetic Resonance Imaging ,Oncology ,Positron emission tomography ,Positron-Emission Tomography ,Female ,business ,Nuclear medicine ,Progressive disease - Abstract
Purpose: To determine the value of diffusion-weighted MRI (DWI-MRI) for treatment response assessment in 2-[18F]fluoro-2-deoxy-D-glucose (FDG)–avid lymphoma. Experimental Design: Patients with FDG-avid Hodgkin (HL) or non-Hodgkin lymphoma (NHL) at pretherapeutic 18F-FDG-PET/CT, who had also undergone pretherapeutic whole-body DWI-MRI, were included in this prospective study. Depending on the histologic lymphoma subtype, patients received different systemic treatment regimens, and follow-up DWI-MRI and 18F-FDG-PET/CT were performed at one or more time points, depending on the clinical course. For each follow-up DWI-MRI, region-based rates of agreement, and rates of agreement in terms of treatment response (complete remission, partial remission, stable disease, or progressive disease), relative to the corresponding 18F-FDG-PET/CT, were calculated. Results: Sixty-four patients were included: 10 with HL, 22 with aggressive NHL, and 32 with indolent NHL. The overall region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.4%. For the 51 interim examinations (performed after 1–3 therapy cycles), region-based agreement of DWI-MRI with 18F-FDG-PET/CT was 99.2%, and for the 48 end-of-treatment examinations, agreement was 99.8%. No significant differences, in terms of region-based agreement between DWI-MRI and 18F-FDG-PET/CT, were observed between the three lymphoma groups (HL, aggressive NHL, indolent NHL; P = 0.25), or between interim and end-of-treatment examinations (P = 0.21). With regard to treatment response assessment, DWI-MRI agreed with 18F-FDG-PET/CT in 99 of 102 follow-up examinations (97.1%), with a κ value of 0.94 (P < 0.0001). Conclusions: In patients with FDG-avid lymphoma, DWI-MRI may be a feasible alternative to 18F-FDG-PET/CT for follow-up and treatment response assessment. Clin Cancer Res; 21(11); 2506–13. ©2015 AACR. more...
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- 2015
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13. Can Interim 18F-FDG PET or Diffusion-Weighted MRI Predict End-of-Treatment Outcome in FDG-Avid MALT Lymphoma After Rituximab-Based Therapy?: A Preliminary Study in 15 Patients
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Werner Dolak, Markus Raderer, Marius E. Mayerhoefer, Matthias Pones, Ingrid Simonitsch-Klupp, Ivo Rausch, Julius Lukas, Georgios Karanikas, Leonhard Müllauer, Kurt Kletter, Michael Weber, and Barbara Kiesewetter more...
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Male ,Lung Neoplasms ,Antineoplastic Agents ,Breast Neoplasms ,Soft Tissue Neoplasms ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Fluorodeoxyglucose F18 ,Stomach Neoplasms ,Interim ,Positron Emission Tomography Computed Tomography ,Multidetector Computed Tomography ,medicine ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Prospective cohort study ,Aged ,medicine.diagnostic_test ,Lacrimal Apparatus Diseases ,business.industry ,Eye Neoplasms ,Splenic Neoplasms ,Remission Induction ,Magnetic resonance imaging ,MALT lymphoma ,General Medicine ,Lymphoma, B-Cell, Marginal Zone ,Middle Aged ,medicine.disease ,Prognosis ,Lymphoma ,Diffusion Magnetic Resonance Imaging ,Treatment Outcome ,Positron emission tomography ,030220 oncology & carcinogenesis ,Positron-Emission Tomography ,Rituximab ,Female ,Immunotherapy ,Lymph Nodes ,Radiopharmaceuticals ,business ,Nuclear medicine ,Progressive disease ,medicine.drug - Abstract
PURPOSE To determine whether interim F-FDG PET or interim diffusion-weighted magnetic resonance imaging (DWI) can predict the end-of-treatment (EOT) outcome after immunotherapy in patients with FDG-avid extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). MATERIALS AND METHODS Patients with untreated MALT lymphoma prospectively underwent whole-body F-FDG PET/CT and DWI before treatment (baseline), and after three cycles (interim) of rituximab-based immunotherapy. Maximum and mean standardized uptake values (SUVmax, SUVmean), and minimum and mean apparent diffusion coefficients (ADCmin, ADCmean), were measured for up to three target lesions per patient. Rates of change between baseline and interim examinations (ΔSUVmax, ΔSUVmean, ΔADCmin, and ΔADCmean) were compared, using ANOVAs, between the four end-of-treatment (EOT, after six cycles of immunotherapy) outcomes: complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD). RESULTS Fifteen patients with 25 lesions were included. Lesion-based post hoc tests showed significant differences between CR and PR for ΔSUVmax (P < 0.001), ΔSUVmean (P < 0.001), and ΔADCmin (P = 0.044), and between CR and SD for ΔSUVmax (P < 0.001), ΔSUVmean (P < 0.001), ΔADCmin (P = 0.021), and ΔADCmean (P = 0.022). No lesion showed PD at EOT. CONCLUSIONS Both quantitative interim F-FDG PET and interim DWI may possibly be useful to predict complete remission at end-of-treatment in MALT lymphoma patients after immunotherapy. more...
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- 2016
14. PET based volume segmentation with emphasis on the iterative TrueX algorithm
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Kurt Kletter, Albert Hirtl, Robert Dudczak, Dietmar Georg, Helmar Bergmann, B. Knäusl, and Georg Dobrozemsky
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Scanner ,Biophysics ,Partial volume ,Iterative reconstruction ,Multimodal Imaging ,Standard deviation ,Imaging phantom ,Imaging, Three-Dimensional ,Fluorodeoxyglucose F18 ,Neoplasms ,Image Processing, Computer-Assisted ,Humans ,Radiology, Nuclear Medicine and imaging ,Segmentation ,Mathematics ,Radiological and Ultrasound Technology ,Phantoms, Imaging ,Radiotherapy Planning, Computer-Assisted ,Radiotherapy Dosage ,Reconstruction algorithm ,Positron-Emission Tomography ,Tomography, X-Ray Computed ,Algorithm ,Algorithms ,Software ,Volume (compression) - Abstract
Purpose To assess the influence of reconstruction algorithms for positron emission tomography (PET) based volume quantification. The specifically detected activity in the threshold defined volume was investigated for different reconstruction algorithms as a function of volume size and signal to background ratio (SBR), especially for volumes smaller than 1 ml. Special attention was given to the Siemens specific iterative reconstruction algorithm TrueX. Methods Measurements were performed with a modified in-house produced IEC body phantom on a Siemens Biograph 64 True Point PET/CT scanner (Siemens, Medical Systems) for six different SBRs (2.1, 3.8, 4.9, 6.7, 8.9, 9.4 and without active background (BG)). The phantom consisted of a water-filled cavity with built-in plastic spheres (0.27, 0.52, 1.15, 2.57, 5.58 and 11.49 ml). The following reconstruction algorithms available on the Siemens Syngo workstation were evaluated: Iterative OSEM (OSEM) (4 iterations, 21 subsets), iterative TrueX (TrueX) (4 iterations, 21 subsets) and filtered backprojection (FBP). For the threshold based volume segmentation the software Rover (ABX, Dresden) was used. Results For spheres larger than 2.5 ml a constant threshold (standard deviation (SD) 10%) level was found for a given SBR and reconstruction algorithm and therefore a mean threshold for the largest three spheres was calculated. This threshold could be approximated by a function inversely proportional to the SBR. The threshold decreased with increasing SBR for all sphere sizes. For the OSEM algorithm the threshold for small spheres with 0.27, 0.52 and 1.15 ml varied between 17% and 44% (depending on sphere size). The threshold for the TrueX algorithm was substantially lower (up to 17%) than for the OSEM algorithm for all sphere sizes. The maximum activity in a specific volume yielded the true activity for the OSEM algorithm when using a SBR independent correction factor C, which depended on sphere size. For the largest three volumes a constant factor C = 1.10 ± 0.03 was found. For smaller volumes, C increased exponentially due to the partial volume effect. For the TrueX algorithm the maximum activity overestimated the true activity. Conclusion The threshold values for PET based target volume segmentation increased with increasing sphere size for all tested algorithms. True activity values of spheres in the phantom could be extracted using experimentally determined correction factors C. The TrueX algorithm has to be used carefully for quantitative comparison (e.g. follow-up) and multicenter studies. more...
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- 2012
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15. Microfluidic preparation of [18F]FE@SUPPY and [18F]FE@SUPPY:2 — comparison with conventional radiosyntheses
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Daniela Haeusler, Robert Dudczak, Cécile Philippe, Markus Mitterhauser, Bernhard K. Keppler, Karem Shanab, L.K. Mien, Helmut Spreitzer, Wolfgang Wadsak, Rupert Lanzenberger, Kurt Kletter, and Johanna Ungersboeck more...
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Reaction conditions ,Fluorine Radioisotopes ,Cancer Research ,Radiochemistry ,Microfluidics ,Nicotinic Acids ,Analytical chemistry ,Microfluidic Analytical Techniques ,A3 ADENOSINE RECEPTOR ,Volumetric flow rate ,chemistry.chemical_compound ,Adenosine a ,chemistry ,Nucleophilic substitution ,Molecular Medicine ,Radiology, Nuclear Medicine and imaging ,Chromatography, Thin Layer ,Fluoride ,Fluoroethyl - Abstract
Introduction Recently, first applications of microfluidic principles for radiosyntheses of positron emission tomography compounds were presented, but direct comparisons with conventional methods were still missing. Therefore, our aims were (1) the set-up of a microfluidic procedure for the preparation of the recently developed adenosine A 3 -receptor tracers [ 18 F]FE@SUPPY [5-(2-[ 18 F]fluoroethyl)2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate] and [ 18 F]FE@SUPPY:2 [5-ethyl-2,4-diethyl-3-((2-[ 18 F]fluoroethyl)sulfanylcarbonyl)-6-phenylpyridine-5-carboxylate] and (2) the direct comparison of reaction conditions and radiochemical yields of the no-carrier-added nucleophilic substitution with [ 18 F]fluoride between microfluidic and conventional methods. Methods For the determination of optimal reaction conditions within an Advion NanoTek synthesizer, 5–50 μl of precursor and dried [ 18 F]fluoride solution were simultaneously pushed through the temperature-controlled reactor (26°C–180°C) with defined reactant bolus flow rates (10–50 μl/min). Radiochemical incorporation yields (RCIYs) and overall radiochemical yields for large-scale preparations were compared with data from conventional batch-mode syntheses. Results Optimal reaction parameters for the microfluidic set-up were determined as follows: 170°C, 30-μl/min pump rate per reactant (reaction overall flow rate of 60 μl/min) and 5-mg/ml precursor concentration in the reaction mixture. Applying these optimized conditions, we observed a significant increase in RCIY from 88.2% to 94.1% ( P n ≥11) for [ 18 F]FE@SUPPY and that from 42.5% to 95.5% ( P n ≥5) for [ 18 F]FE@SUPPY:2 using microfluidic instead of conventional heating. Precursor consumption was decreased from 7.5 and 10 mg to 1 mg per large-scale synthesis for both title compounds, respectively. Conclusion The direct comparison of radiosyntheses data applying a conventional method and a microfluidic approach revealed a significant increase of RCIY using the microfluidic approach. more...
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- 2011
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16. The stability of methyl-, ethyl- and fluoroethylesters against carboxylesterases in vitro: there is no difference
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Daniela Haeusler, Robert Dudczak, Wolfgang Wadsak, Karl-Heinz Wagner, Kurt Kletter, Markus Mitterhauser, and Lukas Nics
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Cancer Research ,Chemistry ,Stereochemistry ,Carboxylic Acids ,Statistical difference ,Esters ,Limiting ,Michaelis–Menten kinetics ,In vitro ,Carboxylesterase ,Substrate Specificity ,Enzyme catalysis ,Kinetics ,Drug Stability ,Standard protocol ,Molecular Medicine ,Substrate specificity ,Radiology, Nuclear Medicine and imaging ,Radioactive Tracers - Abstract
Introduction Carboxylesterases (CES) play a very important role in the hydrophilic biotransformation of a huge number of structurally diverse drugs and especially play a leading part in the catabolic pathway of carboxylesters or thioesters. Hence, the aim of the present study was the comparison of the in vitro stability of methyl- and ethylesters with fluoroethylesters. Methods We incubated methyl 3β-(4-iodophenyl)tropane-2β-carboxylate (β-CIT)/2-fluoroethyl 3β-(4-iodophenyl)tropane-2β-carboxylate (FE@CIT), methyl 1-(1-phenylethyl)-1 H -imidazole-5-carboxylate (MTO)/ethyl 1-(1-phenylethyl)-1 H -imidazole-5-carboxylate (ETO)/2-fluoroethyl 1-(1-phenylethyl)-1 H -imidazole-5-carboxylate (FETO), ethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4 H -benzo-[f]imidazo[1,5-a]-[1,4]diazepine-3-carboxylate (FMZ)/2-fluoroethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4 H -benzo-[f]imidazo[1,5-a]-[1,4]diazepine-3-carboxylate (FFMZ), methyl 1-phenylethyl-4-( N -propanoylanilino)piperidine-4-carboxylate (CFN)/2-fluoroethyl 1-phenylethyl-4-( N -propanoylanilino)piperidine-4-carboxylate (FE@CFN) and methyl 2,4-diethyl-3-methylsulfanylcarbonyl-6-phenylpyridine-5-carboxylate [(Me) 2 @SUPPY]/2-fluorethyl 2,4-diethyl-3-ethylsulfanylcarbonyl-6-phenylpyridine-5-carboxylate (FE@SUPPY) under physiological conditions. The enzymatic reactions were stopped at different time points and analyzed by a standard protocol. Results The Michaelis–Menten constants ( K M ) and limiting velocities ( V max ) are comparable. The statistical K M values were as follows: β-CIT/FE@CIT, P >.05; MTO/FETO, P >.06; ETO/FETO, P >.09; FMZ/FFMZ, P >.05; CFN/FE@CFN, P >.9; (Me) 2 @SUPPY/FE@SUPPY, P >.07. Conclusion We found no statistical difference in stability against CES in vitro. These findings support the strategy to translate C-11-methyl-/ethylesters into their longer-lived F-18-fluoroethyl analogues. more...
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- 2011
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17. Evaluating repetitive18F-fluoroazomycin-arabinoside (18FAZA) PET in the setting of MRI guided adaptive radiotherapy in cervical cancer
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Matthias Schuetz, Dobrica Lukic, Robert Dudczak, Spyridoula Kommata, Georgios Karanikas, Kurt Kletter, Johannes Dimopoulos, Maximilian Schmid, Barbara Bachtiary, Dietmar Georg, and Richard Pötter
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Adult ,Periodicity ,medicine.medical_specialty ,medicine.medical_treatment ,Brachytherapy ,Adaptation, Biological ,Uterine Cervical Neoplasms ,Pilot Projects ,Adenocarcinoma ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Adaptive radiotherapy ,Aged ,Aged, 80 and over ,Cisplatin ,Cervical cancer ,medicine.diagnostic_test ,business.industry ,Radiotherapy Dosage ,Magnetic resonance imaging ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Radiotherapy, Computer-Assisted ,Radiography ,18F-Fluoroazomycin Arabinoside ,Oncology ,Nitroimidazoles ,Positron emission tomography ,Positron-Emission Tomography ,Concomitant ,Carcinoma, Squamous Cell ,Female ,Radiology ,Nuclear medicine ,business ,medicine.drug - Abstract
The aim of this pilot study was to assess tumour hypoxia in patients with cervical cancer before, during and after combined radio-chemotherapy and Magnetic Resonance Imaging (MRI) guided brachytherapy (BT) by use of the hypoxia Positron Emission Tomography (PET) tracer (18)F-fluoroazomycin-arabinoside ((18)FAZA ).Fifteen consecutive patients with locally advanced cervical cancer referred for definitive radiotherapy (RT) were included in an approved clinical protocol. Stage distribution was 3 IB1, 1 IB2, 10 IIB, 1 IIIB, tumour volume was 55 cm(3) (+/- 67, SD). Dynamic and static (18)FAZA -PET scans were performed before, during and after external beam therapy (EBRT) and image guided BT +/- concomitant cisplatin. Dose was prescribed to the individual High Risk Clinical Target Volume (HR CTV) taking into account the dose volume constraints for adjacent organs at risk.Five patients had visually identifiable tumours on (18)FAZA -PET scans performed prior to radio-chemotherapy and four patients before brachytherapy. One of five (18)FAZA PET positive patients had incomplete remission three months after RT, one had regional recurrence. Four of ten (18)FAZA-PET negative patients developed distant metastases. The one patient with incomplete remission received 69 Gy (D90) in the HR CTV, whereas all other patients received mean 99 Gy (+/-12, SD).PET imaging with (18)FAZA is feasible in patients with cancer of the uterine cervix. However, its predictive and prognostic value remains to be clarified. This applies in particular for the additional value of (18)FAZA-PET compared to morphologic repetitive MRI within the setting of image guided high dose radiotherapy which may contribute to overcome hypoxia related radioresistance. more...
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- 2010
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18. Cortisol plasma levels in social anxiety disorder patients correlate with serotonin-1A receptor binding in limbic brain regions
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Kurt Kletter, Christoph Spindelegger, Siegfried Kasper, Elena Akimova, Andreas Hahn, M. Fink, L.K. Mien, Wolfgang Wadsak, Rupert Lanzenberger, Georg S. Kranz, Markus Mitterhauser, Markus Savli, and U. Moser more...
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Adult ,Male ,medicine.medical_specialty ,Hydrocortisone ,Pyridines ,Hippocampus ,Serotonergic ,Amygdala ,Piperazines ,Young Adult ,Dorsal raphe nucleus ,Retrosplenial cortex ,Internal medicine ,Limbic System ,medicine ,Humans ,Pharmacology (medical) ,Radionuclide Imaging ,5-HT receptor ,Pharmacology ,medicine.disease ,Anxiety Disorders ,Psychiatry and Mental health ,Endocrinology ,medicine.anatomical_structure ,Phobic Disorders ,Mood disorders ,Receptor, Serotonin, 5-HT1A ,Serotonin Antagonists ,Radiopharmaceuticals ,Psychology ,Neuroscience ,Glucocorticoid ,medicine.drug - Abstract
Dysregulation of the hypothalamic-pituitary-adrenocortical axis with deficient glucocorticoid feedback and alterations in the serotonergic system have been identified as biological correlates of mood disorders. Close examination of the interaction between these systems may offer insights into the pathophysiology of anxiety disorders and depression to understand how stress and these disorders are related. In this study, we investigated the relationship between plasma levels of cortisol and the dominant inhibitory serotonergic receptor, serotonin-1A (5-HT1A). Using positron emission tomography (PET) and the radioligand [carbonyl-11C]WAY-100635, we quantified the 5-HT1A receptor binding. Data from 12 male patients with social phobia and 18 matched control subjects were analysed. Seven brain regions were investigated: the anterior and posterior cingulate cortices, hippocampus, amygdala, medial orbitofrontal and retrosplenial cortices, and dorsal raphe nucleus. Partial correlation analysis, controlled for age and radiochemical variables, was performed to demonstrate the association between cortisol plasma levels and 5-HT1A receptor binding. Cortisol plasma levels were significantly lower in patients with social phobia compared to healthy controls. Moreover, we found strong negative correlations between cortisol plasma levels and 5-HT1A binding in the amygdala (r=-0.93, p=0.0004), hippocampus (r=-0.80, p=0.009), and retrosplenial cortex (r=-0.48, p=0.04) in patients with social phobia. Within the former two regions, these associations were significantly higher in patients than in healthy controls. This PET study confirms a negative association between plasma cortisol levels and the 5-HT1A receptor distribution consistent with studies in rodents and non-human primates. Dysregulation of the cortisol level might increase the vulnerability for mood disorders by altering limbic 5-HT1A receptors. more...
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- 2010
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19. Hypothalamic serotonin-1A receptor binding measured by PET predicts the plasma level of dehydroepiandrosterone sulfate in healthy women
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Wolfgang Wadsak, U. Moser, Rupert Lanzenberger, Markus Mitterhauser, Christian Bieglmayer, L.K. Mien, Christoph Spindelegger, Siegfried Kasper, and Kurt Kletter
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Adult ,endocrine system ,medicine.medical_specialty ,Hydrocortisone ,Pyridines ,Hypothalamus ,Hippocampus ,Serotonergic ,Piperazines ,Young Adult ,chemistry.chemical_compound ,Dehydroepiandrosterone sulfate ,Dorsal raphe nucleus ,Predictive Value of Tests ,Internal medicine ,polycyclic compounds ,medicine ,Radioligand ,Humans ,Carbon Radioisotopes ,5-HT receptor ,Dehydroepiandrosterone Sulfate ,General Neuroscience ,Human brain ,medicine.anatomical_structure ,Endocrinology ,nervous system ,chemistry ,Positron-Emission Tomography ,Receptor, Serotonin, 5-HT1A ,Female ,Radiopharmaceuticals ,Psychology ,hormones, hormone substitutes, and hormone antagonists ,Blood sampling - Abstract
Serotonin modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis particularly via the serotonin-1A receptor (5-HT(1A)). Therefore, the rationale of this positron emission tomography (PET) study was to investigate the influence of the 5-HT(1A) receptor distribution in the human brain on plasma levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol in vivo. Eighteen healthy female were measured with PET and the selective 5-HT(1A) receptor radioligand [carbonyl-(11)C]WAY-100635. Nine a priori defined brain regions (hypothalamus, orbitofrontal cortex, amygdala, hippocampus, anterior and posterior cingulate cortices, dorsal raphe nucleus, retrosplenial cortex, and insula) and the cerebellum (reference region) were delineated on coregistered MR images. DHEAS and cortisol plasma levels were collected by blood sampling in the morning of the PET day. Linear regression analysis of DHEAS plasma level as dependent variable and hypothalamic 5-HT(1A) receptor binding potential (BP) as independent variable showed a highly significant association (r=.691, p=.002). The hypothalamic 5-HT(1A) BP predicted 47.7% of the variability in DHEAS plasma levels. Regressions were borderline significant (p.01, Bonferroni corrected threshold.0056) between 5-HT(1A) BP in the anterior cingulate and orbitofrontal cortices and free cortisol levels. No significant associations between DHEAS or cortisol and the 5-HT(1A) receptor BP in other investigated brain regions were found. In conclusion, the serotonergic system may influence the DHEAS plasma level by modulating CRH and ACTH release via hypothalamic 5-HT(1A) receptors as reported for cortisol before. As disturbances of the HPA axis as well as changes of the 5-HT(1A) receptor distribution have been reported in affective disorders, future studies should focus on these interactions. more...
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- 2010
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20. 'Label and go' – A fast and easy radiolabelling method for pellets
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Leonhard-Key Mien, B. Knäusl, Helmut Viernstein, Wolfgang Wadsak, Cécile Philippe, Kurt Kletter, Markus Mitterhauser, S. Salar-Behzadi, and Robert Dudczak
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Fluorine Radioisotopes ,Radiation ,Chromatography ,Chemistry ,Radiochemistry ,Pellets ,Tracking (particle physics) ,chemistry.chemical_compound ,Fluidized bed ,Isotope Labeling ,Positron-Emission Tomography ,Pellet ,Technology, Pharmaceutical ,Particle ,Process optimization ,Ion Exchange Resins ,Cellulose ,Ion-exchange resin ,Fluoride - Abstract
For the development and process optimization of pharmaceutical equipment, it is important to investigate the underlying processes. Taking the fluidized bed technology as an example, the study of particle flow pattern and convection of the particles within the functional unity is essential for construction and process improvement. With positron emission particle tracking (PEPT) it is possible to study the real-time particle motion with radiolabelled particles. We established a fast and simple labelling technique with [(18)F]fluoride for pellets composed of Avicel and anion exchange resin. The uptake of activity ranged from 1.3% to 1.7% per mg and 8.6% to 16.3% per pellet. A specific binding of [(18)F]fluoride with increasing degree of anion exchange resin in the pellets could be observed. more...
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- 2010
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21. Diagnostic imaging in Merkel cell carcinoma: Lessons to learn from 16 cases with correlation of sonography, CT, MRI and PET
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Kurt Kletter, Michael Weber, Clemens Novotny, Robert Dudczak, Alexander Becherer, Philipp Peloschek, Christian Czerny, Christina Mueller-Mang, Johannes Sailer, and Markus Dawid
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Male ,medicine.medical_specialty ,Skin Neoplasms ,medicine.medical_treatment ,Statistics as Topic ,Sensitivity and Specificity ,Fluorodeoxyglucose F18 ,Biopsy ,medicine ,Medical imaging ,Carcinoma ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Aged, 80 and over ,Fluorodeoxyglucose ,medicine.diagnostic_test ,Merkel cell carcinoma ,business.industry ,Reproducibility of Results ,General Medicine ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Carcinoma, Merkel Cell ,Positron emission tomography ,Positron-Emission Tomography ,Female ,Histopathology ,Lymphadenectomy ,Radiology ,Radiopharmaceuticals ,Tomography, X-Ray Computed ,business ,Nuclear medicine ,medicine.drug - Abstract
Objective The authors report imaging findings in a series of 16 patients with MCC, a rare tumour which is often managed primarily by a dermatologist. To our knowledge, no equivalent series of MCC has been described in the nuclear medicine literature. Material and Methods In this IRB-approved retrospective noncomparative case series 16 patients with biopsy-proven Merkel cell carcinoma were included between January 1999 and October 2007. Twenty-nine whole body PET scans (18F-FDG n = 24, 18F-FDOPA n = 5) in 16 patients were retrospectively reviewed with regard to tracer uptake in six anatomical sites per patient. For 127/144 of FDG-PET evaluated regions and 68/144 of regions depicted by conventional imaging methods, a valid standard of reference could be obtained. A combined standard of reference was applied, which consisted of histopathology (lymphadenectomy or biopsy) or clinical or radiological follow-up for at least 12 months. Results: the mean FDG uptake over the clinicopatholigical verified FDG avid areas was 4.7 SUV (1.5–9.9 SUV). The region based assessment of diagnostic value, in consideration of the standard of reference, resulted in a sensitivity of 85.7% and a specificity of 96.2% of FDG-PET (n = 127) and in a combined sensitivity of 95.5% and a specificity of 89.1% for morphological imaging methods (n = 68). Differences between methods did not reach statistical significance (p = 1.00, p = 0.18). Conclusions FDG-PET is a highly useful whole body staging method of comparable value compared to conventional imaging methods with restricted field of view. The lessons learned from case series are discussed. more...
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- 2010
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22. Aggression is related to frontal serotonin-1A receptor distribution as revealed by PET in healthy subjects
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U. Moser, M. Fink, Kurt Kletter, Agnes Flöel, Andreas Hahn, Markus Savli, L.K. Mien, Markus Mitterhauser, A. Veronica Witte, Wolfgang Wadsak, Rupert Lanzenberger, Christoph Spindelegger, Siegfried Kasper, and P. Stein more...
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Adult ,Male ,medicine.medical_specialty ,Pyridines ,Central nervous system ,Poison control ,Personality Assessment ,Piperazines ,chemistry.chemical_compound ,Sex Hormone-Binding Globulin ,Surveys and Questionnaires ,Internal medicine ,medicine ,Humans ,Distribution (pharmacology) ,Testosterone ,Radiology, Nuclear Medicine and imaging ,Carbon Radioisotopes ,Prefrontal cortex ,Neurotransmitter ,Research Articles ,Brain Mapping ,Estradiol ,Radiological and Ultrasound Technology ,Aggression ,Healthy subjects ,Brain ,Magnetic Resonance Imaging ,Kinetics ,medicine.anatomical_structure ,Endocrinology ,Neurology ,chemistry ,Positron-Emission Tomography ,Receptor, Serotonin, 5-HT1A ,Female ,Neurology (clinical) ,Serotonin ,Anatomy ,medicine.symptom ,Psychology - Abstract
Objectives: Various studies indicate that serotonin regulates impulsivity and the inhibitory control of aggression. Aggression is also known to be modified by sex hormones, which exert influence on serotonergic neurotransmission. The present study aimed to elucidate potential interactions between human aggression, the inhibitory serotonergic 5‐HT(1A) receptor, and sex hormones. Experimental Design: Thirty‐three healthy volunteers (16 women, aged 26.24 ± 5.5 yr) completed a validated questionnaire incorporating five dimensions of aggression. Subsequently, all subjects underwent positron emission tomography with the radioligand [carbonyl‐(11)C]WAY‐100635 to quantify 5‐HT(1A) binding potentials (BP(ND)s) in the prefrontal cortex, limbic areas, and midbrain. Also, plasma levels of testosterone, 17ß‐estradiol and sex hormone‐binding globulin (SHBG) were measured. Relations between aggression scores, regional 5‐HT(1A) BP(ND)s, and hormone levels were analyzed using correlations, multivariate analyses of variance, and linear regressions. Principal Observations: Statistical analyses revealed higher 5‐HT(1A) receptor BP(ND)s in subjects exhibiting higher aggression scores in prefrontal (all P < 0.041) and anterior cingulate cortices (P = 0.016). More aggressive subjects were also characterized by lower SHBG levels (P = 0.015). Moreover, higher SHBG levels were associated with lower 5‐HT(1A) BP(ND)s in frontal (P = 0.048) and cingulate cortices (all P < 0.013) and in the amygdala (P = 0.03). Conclusions: The present study provides first‐time evidence for a specific interrelation between the 5‐HT(1A) receptor distribution, sex hormones, and aggression in humans. Our findings point to a reduced down‐stream control due to higher amounts or activities of frontal 5‐HT(1A) receptors in more aggressive subjects, which is presumably modulated by sex hormones. Hum Brain Mapp 30:2558–2570, 2009. © 2008 Wiley‐Liss, Inc. more...
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- 2009
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23. Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET
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Claudia C. Wagner, Kurt Kletter, Markus Müller, Martin Bauer, Rudolf Karch, Aiman Abrahim, Friederike Neumann, Oliver Langer, Markus Zeitlinger, University of Zurich, and Langer, O
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Adult ,Male ,Aging ,Vasodilator Agents ,610 Medicine & health ,Statistical parametric mapping ,030226 pharmacology & pharmacy ,Article ,03 medical and health sciences ,0302 clinical medicine ,Region of interest ,Cerebellum ,medicine ,2736 Pharmacology (medical) ,Humans ,Pharmacology (medical) ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Carbon Radioisotopes ,Aged ,Pharmacology ,Volume of distribution ,Cerebral Cortex ,medicine.diagnostic_test ,business.industry ,Brain atlas ,Age Factors ,Brain ,General Medicine ,Middle Aged ,Amygdala ,Frontal Lobe ,medicine.anatomical_structure ,3004 Pharmacology ,Frontal lobe ,Verapamil ,Cerebral cortex ,Positron emission tomography ,Blood-Brain Barrier ,Positron-Emission Tomography ,Female ,10029 Clinic and Policlinic for Internal Medicine ,Nuclear medicine ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Purpose The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier. Methods Seven young (mean age: 27±4 years) and six elderly (mean age: 69±9 years) healthy volunteers underwent dynamic (R)-[ 11 C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM). Brain regions that SPM analysis had shown to be most affected by age were analysed by a region of interest (ROI)-based approach using a maximum probability brain atlas, before and after partial volume correction (PVC). Results SPM analysis revealed significant clusters of DV increases in cerebellum, temporal and frontal lobe of elderly compared to younger subjects. In the ROI-based analysis, elderly subjects showed significant DV increases in amygdala (+30%), insula (+26%) and cerebellum (+25%) before PVC, and in insula (+33%) after PVC. Conclusions Increased VPM DV values in the brains of elderly subjects suggest a decrease in cerebral P-gp function with increasing age. more...
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- 2009
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24. Chronic heart failure leads to an expanded plasma volume and pseudoanaemia, but does not lead to a reduction in the body's red cell volume
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Spyridoula Kommata, Christian Bieglmayer, Guido Strunk, Thomas Szekeres, Christopher Adlbrecht, Richard Pacher, Rudolf Berger, Deddo Mörtl, Gerald Maurer, Georgios Karanikas, Kurt Kletter, Martin Hülsmann, and Irene M. Lang more...
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Male ,medicine.medical_specialty ,Anemia ,Iron ,Renal function ,Gastroenterology ,Hemoglobins ,Internal medicine ,medicine ,Humans ,Plasma Volume ,Erythropoietin ,Erythrocyte Volume ,Heart Failure ,Anemia, Iron-Deficiency ,business.industry ,Iron deficiency ,Middle Aged ,medicine.disease ,Red blood cell ,Cross-Sectional Studies ,medicine.anatomical_structure ,Endocrinology ,Heart failure ,Chronic Disease ,Circulatory system ,Female ,Hemoglobin ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Aims Chronic heart failure (CHF) is frequently associated with a decreased haemoglobin level, whereas the mechanism remains largely unknown. Methods and results One hundred consecutive CHF patients without anaemia or renal dysfunction based on non-cardiac reasons were enrolled. We explored determinants of anaemia (as iron parameters, erythropoietin, hepcidin and kidney function) including red cell volume (RCV) (by a 51 Cr assay) as well as related markers and plasma volume. The influence of each factor on haemoglobin concentrations was determined in a multiple regression model. Mean haemoglobin concentrations were 11.7 +/- 0.8 mg/dL in anaemic CHF patients and 14.4 +/- 1.2 mg/dL in non-anaemic patients. Corrected reticulocytes were lower in anaemic patients (35.1 +/- 15.7 vs. 50.3 +/- 19.2 G/L, P = 0.001), but the RCV was not reduced (1659.3 +/- 517.6 vs. 1826.4 +/- 641.3 mL, P = 0.194). We found that plasma volumes were significantly higher in anaemic CHF patients (70.0 +/- 2.4 vs. 65.0 +/- 4.0%, P0.001). Plasma volume was the best predictor of haemoglobin concentrations in the regression model applied (B = -0.651, P0.001, R(2) = 0.769). Conclusion Haemodilution appears to be the most potent factor for the development of low haemoglobin levels in patients with CHF. Our data support an additional independent, but minor influence of iron deficiency on haemoglobin concentrations in CHF patients. more...
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- 2008
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25. The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-11C]WAY-100635
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Robert Dudczak, P. Stein, U. Moser, Markus Savli, Markus Mitterhauser, M. Fink, Kurt Kletter, Wolfgang Wadsak, Rupert Lanzenberger, Christoph Spindelegger, Siegfried Kasper, and Leonhard-Key Mien
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Adult ,Male ,Aging ,medicine.medical_specialty ,Pyridines ,Serotonergic ,Piperazines ,Internal medicine ,Humans ,Medicine ,Distribution (pharmacology) ,Radiology, Nuclear Medicine and imaging ,Receptor ,Depression (differential diagnoses) ,Sex Characteristics ,medicine.diagnostic_test ,business.industry ,General Medicine ,Endocrinology ,Follicular Phase ,Social Class ,Health ,Positron emission tomography ,Positron-Emission Tomography ,Receptor, Serotonin, 5-HT1A ,5-HT1A receptor ,Anxiety ,Female ,Serotonin ,medicine.symptom ,business - Abstract
The higher prevalence rates of depression and anxiety disorders in women compared to men have been associated with sexual dimorphisms in the serotonergic system. The present positron emission tomography (PET) study investigated the influence of sex on the major inhibitory serotonergic receptor subtype, the serotonin-1A (5-HT(1A)) receptor.Sixteen healthy women and 16 healthy men were measured using PET and the highly specific radioligand [carbonyl-(11)C]WAY-100635. Effects of age or gonadal hormones were excluded by restricting the inclusion criteria to young adults and by controlling for menstrual cycle phase. The 5-HT(1A) receptor BP(ND) was quantified using (1) the 'gold standard' manual delineation approach with ten regions of interest (ROIs) and (2) a newly developed delineation method using a PET template normalized to the Montreal Neurologic Institute space with 45 ROIs based on automated anatomical labeling.The 5-HT(1A) receptor BP(ND) was found equally distributed in men and women applying both the manual delineation method and the automated delineation approach. Women had lower mean BP(ND) values in every region investigated, with a borderline significant sex difference in the hypothalamus (p = 0.012, uncorrected). There was a high intersubject variability of the 5-HT(1A) receptor BP(ND) within both sexes compared to the small mean differences between men and women.To conclude, when measured in the follicular phase, women do not differ from men in the 5-HT(1A) receptor binding. To explain the higher prevalence of affective disorders in women, further studies are needed to evaluate the relationship between hormonal status and the 5-HT(1A) receptor expression. more...
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- 2008
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26. Multimodal imaging of human early visual cortex by combining functional and molecular measurements with fMRI and PET
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A. Holik, Ewald Moser, Wolfgang Wadsak, F. Gerstl, Rupert Lanzenberger, Markus Mitterhauser, Siegfried Kasper, Kurt Kletter, and Christian Windischberger
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Adult ,Male ,Brain Mapping ,medicine.diagnostic_test ,Cognitive Neuroscience ,Human brain ,Magnetic Resonance Imaging ,Brain mapping ,medicine.anatomical_structure ,Visual cortex ,Neurology ,Cerebral cortex ,Neurotransmitter receptor ,Positron-Emission Tomography ,Cortex (anatomy) ,medicine ,Radioligand ,Humans ,Female ,Psychology ,Functional magnetic resonance imaging ,Receptors, Serotonin, 5-HT1 ,Neuroscience ,Visual Cortex - Abstract
Receptor distribution patterns of neurotransmitters and distinct functional fields of the human brain appear to be tightly connected with respect to their topological allocation along the cerebral cortex. There is, however, considerable lack of human data directly demonstrating this association in vivo. Here, we assessed the relationship between the distribution of the major inhibitory serotonergic neurotransmitter receptor, the 5-HT(1A) subtype, and the functional organization within early visual cortex defined by retinotopic mapping. The 5-HT(1A) receptor-binding potential was quantified by positron emission tomography (PET) using the highly selective and specific radioligand [carbonyl-(11)C]WAY-100635 in seven healthy subjects. The retinotopic maps and borders determined by functional magnetic resonance imaging (fMRI) were compared to the receptor distribution employing surface-based region of interest analysis in each of these subjects. We found a significant difference in receptor-binding potential in the functionally defined primary (V1) compared to secondary (V2) visual area, as V1 exhibits only 68% of receptor binding found in V2 in both hemispheres, which is consistent with postmortem data. Our in vivo findings clearly support prior assumptions of a link between receptor distribution and functional fields of the human cortex. more...
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- 2008
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27. No Immunological Benefit of Selenium in Consecutive Patients with Autoimmune Thyroiditis
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Robert Schoen, Anna Antoni, Georgios Karanikas, Kurt Kletter, Matthias Schuetz, Heying Duan, Sylvester Kontur, Robert Dudczak, Spyridoula Kommata, and Martin Willheim
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Adult ,CD4-Positive T-Lymphocytes ,endocrine system ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,chemistry.chemical_element ,CD8-Positive T-Lymphocytes ,Iodide Peroxidase ,Severity of Illness Index ,Thyroglobulin ,Antioxidants ,Thyroiditis ,law.invention ,Autoimmune thyroiditis ,Interferon-gamma ,Selenium ,fluids and secretions ,Endocrinology ,Randomized controlled trial ,Thyroid peroxidase ,law ,Severity of illness ,medicine ,Humans ,Aged ,Autoantibodies ,Aged, 80 and over ,biology ,Tumor Necrosis Factor-alpha ,business.industry ,Thyroiditis, Autoimmune ,food and beverages ,Middle Aged ,medicine.disease ,chemistry ,embryonic structures ,Immunology ,biology.protein ,Interleukin-2 ,Female ,business - Abstract
Recently it has been demonstrated that after selenium (Se) supplementation in autoimmune thyroiditis (AIT) patients, there was a significant decrease of thyroid peroxidase (TPO) autoantibody (TPOAb) levels. The aim of our study was to evaluate the immunological benefit of Se administration in unselected AIT patients and thus address the question whether Se administration should generally be recommended for AIT patients.Thirty-six consecutive AIT patients (aged 19-85 years) were included in the present study. In addition to their levothyroxine (LT(4)) treatment, 18 patients received 200 microg (2.53 micromol) sodium selenite per day orally for the time span of 3 months, whereas 18 patients received placebo. All patients had measurement of thyroid hormones, thyrotropin (TSH), autoantibodies (thyroglobulin antibodies [TgAb] and TPOAb), Se levels, and intracellular cytokine detection in CD4(+) and CD8(+) T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry before and after Se or placebo administration.No significant difference in the TPOAb levels was found after Se administration (524 +/- 452 vs. 505 +/- 464 IU/mL; p0.05). Furthermore, we found no significant differences in the CD4(+) or CD8(+) cytokine pattern (IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, TNF-beta) in patients before and after Se administration, in patients before and after placebo administration and between Se group and placebo group before and after Se vs. placebo administration.We demonstrate that Se administration in our AIT patient's cohort does not induce significant immunological changes, either in terms of cytokine production patterns of peripheral T lymphocytes or of TPOAb levels. Our data suggest that AIT patients with moderate disease activity (in terms of TPOAb and cytokine production patterns) may not (equally) benefit as patients with high disease activity. more...
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- 2008
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28. Preparation and first evaluation of [18F]FE@SUPPY: a new PET tracer for the adenosine A3 receptor
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Robert Dudczak, Bernhard K. Keppler, Helmut Spreitzer, Leonhard-Key Mien, Wolfgang Wadsak, Rupert Lanzenberger, Karoline Sindelar, Daniela Haeusler, Helmut Viernstein, Kurt Kletter, Dagmar E. Ettlinger, Markus Mitterhauser, and Karem Shanab more...
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Male ,Agonist ,Fluorine Radioisotopes ,Cancer Research ,Biodistribution ,medicine.medical_specialty ,medicine.drug_class ,Pharmacology ,Rats, Sprague-Dawley ,Internal medicine ,medicine ,Radioligand ,Animals ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,Rats, Wistar ,Receptor ,Chemistry ,Receptor, Adenosine A3 ,Radiosynthesis ,Nicotinic Acids ,Adenosine A3 receptor ,Ligand (biochemistry) ,Adenosine ,Rats ,Endocrinology ,Positron-Emission Tomography ,Autoradiography ,Molecular Medicine ,Radiopharmaceuticals ,medicine.drug - Abstract
Introduction Changes of the adenosine A 3 receptor subtype (A3AR) expression have been shown in a variety of pathologies, especially neurological and affective disorders, cardiac diseases and oncological and inflammation processes. Recently, 5-(2-fluoroethyl) 2,4-diethyl-3-(ethylsulfanylcarbonyl)-6-phenylpyridine-5-carboxylate (FE@SUPPY) was presented as a high-affinity ligand for the A3AR with good selectivity. Our aims were the development of a suitable labeling precursor, the establishment of a reliable radiosynthesis for the fluorine-18-labeled analogue [ 18 F]FE@SUPPY and a first evaluation of [ 18 F]FE@SUPPY in rats. Methods [ 18 F]FE@SUPPY was prepared in a feasible and reliable manner by radiofluorination of the corresponding tosylated precursor. Biodistribution was carried out in rats, and organs were removed and counted. Autoradiography was performed on rat brain slices in the presence or absence of 2-Cl-IB-MECA. Results Overall yields and radiochemical purity were sufficient for further preclinical and clinical applications. The uptake pattern of [ 18 F]FE@SUPPY found in rats mainly followed the described mRNA distribution pattern of the A3AR. Specific uptake in brain was demonstrated by blocking with a selective A3AR agonist. Conclusion We conclude that [ 18 F]FE@SUPPY has the potential to serve as the first positron emission tomography tracer for the A3AR. more...
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- 2008
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29. Radiologie in einem prägraduellen problembasiert-integrierten Medizincurriculum
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Franz Kainberger and Kurt Kletter
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Medical education ,business.industry ,Process (engineering) ,Teaching method ,media_common.quotation_subject ,education ,Core competency ,Computer-Assisted Instruction ,Paradigm shift ,Medical imaging ,Medicine ,Radiology, Nuclear Medicine and imaging ,business ,Function (engineering) ,Curriculum ,media_common - Abstract
Pregraduate medical curricula are currently undergoing a reform process that is moving away from a traditional discipline-related structure and towards problem-based integrated forms of teaching. Imaging sciences, with their inherently technical advances, are specifically influenced by the effects of paradigm shifts in medical education. The teaching of diagnostic radiology should be based on the definition of three core competencies: in vivo visualization of normal and abnormal morphology and function, diagnostic reasoning, and interventional treatment. On the basis of these goals, adequate teaching methods and e-learning tools should be implemented by focusing on case-based teaching. Teaching materials used in the fields of normal anatomy, pathology, and clinical diagnosis may help diagnostic radiology to play a central role in modern pregraduate curricula. more...
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- 2007
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30. Simple and fully automated preparation of [carbonyl-11C]WAY-100635
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Wolfgang Wadsak, Dagmar E. Ettlinger, Markus Mitterhauser, Rupert Lanzenberger, Robert Dudczak, Kurt Kletter, Leonhard-Key Mien, and Daniela Haeusler
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Fully automated ,Chemistry ,Radiosynthesis ,Nanotechnology ,Physical and Theoretical Chemistry ,Receptor ,Combinatorial chemistry - Abstract
Summary. So far, [carbonyl- 11 C]WAY-100635 is the PET-tracer of choice for 5HT 1A -receptor-imaging. Since thepreparation is still a challenge, we aimed at (1) the eval-uation of various essential parameters for the successfulpreparation, (2) the simplification of the radiosynthesis and(3) the establishment of a safe and fully automated system.The preparation is based on a commercial synthesizer andall chemicals are used without further processing. We founda low failure rate (7 . 7%), high average yield (4 . 0±1 . 0GBq)and a specific radioactivity of 292 ±168 GBq / µmol (both atthe end of synthesis, EOS). Introduction Carbon-11 labelled WAY-100635 ( N -(2-(1-(4-(2-methoxy-phenyl)-1-piperazinyl)ethyl))- N -(2-pyridyl)-cyclohexane-carboxamide; WAY) was introduced into positron emis-sion tomography (PET) as a highly potent and selectiveantagonist at the 5HT 1A receptors more than a decade ago.Since 5HT 1A receptors are implicated in the pathogenesisof anxiety, depression, eating disorders and motion sick-ness, they are an important target for drug therapy [1,2].The visualisation and quantification of this receptor is a ba-sis for further exploration of molecular pathologies causingpsychiatric conspicuousness. The most extensively studiedtracers are two carbon-11 labelled WAY-100635 derivatives,[O-methyl more...
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- 2007
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31. Pharmacoresistance in Epilepsy: A Pilot PET Study with the P-Glycoprotein Substrate R -[11 C]verapamil
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Martin Bauer, Aiman Abrahim, Raute Sunder-Plassmann, Alexander Hammers, Rudolf Karch, Matthias J. Koepp, Gert Luurtsema, Christoph Baumgartner, Markus Müller, Christian Joukhadar, Robert Dudczak, Oliver Langer, Kurt Kletter, Stephan Gentzsch, Martin Brunner, Friedrich Zimprich, and Ekaterina Pataraia more...
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medicine.medical_specialty ,Chemistry ,Hippocampal formation ,medicine.disease ,Epileptogenesis ,Temporal lobe ,Central nervous system disease ,Epilepsy ,Cerebrospinal fluid ,Endocrinology ,Neurology ,Anesthesia ,Internal medicine ,medicine ,Verapamil ,Choroid plexus ,Neurology (clinical) ,medicine.drug - Abstract
Purpose and Methods: Regional overexpression of the multidrug transporter P-glycoprotein (P-gp) in epileptic brain tissue may lower target site concentrations of antiepileptic drugs and thus contribute to pharmacoresistance in epilepsy. We used the P-gp substrate R-[(11)C]verapamil and positron emission tomography (PET) to test for differences in P-gp activity between epileptogenic and nonepileptogenic brain regions of patients with drug-resistant unilateral temporal lobe epilepsy (n = 7). We compared R-[(11)C]verapamil kinetics in homologous brain volumes of interest (VOIs) located ipsilateral and contralateral to the seizure focus. Results: Among different VOIs, radioactivity was highest in the choroid plexus. The hippocampal VOI could not be used for data analysis because it was contaminated by spill-in of radioactivity from the adjacent choroid plexus. In several other temporal lobe regions that are known to be involved in seizure generation and propagation ipsilateral influx rate constants K(1) and efflux rate constants k(2) of R-[(11)C]verapamil were descriptively increased as compared to the contralateral side. Parameter asymmetries were most prominent in parahippocampal and ambient gyrus (K(1), range: -3.8% to +22.3%; k(2), range: -2.3% to +43.9%), amygdala (K(1), range: -20.6% to +31.3%; k(2), range: -18.0% to +38.9%), medial anterior temporal lobe (K(1), range: -8.3% to +14.5%; k(2), range: -14.5% to +31.0%) and lateral anterior temporal lobe (K(1), range: -20.7% to +16.8%; k(2), range: -24.4% to +22.6%). In contrast to temporal lobe VOIs, asymmetries were minimal in a region presumably not involved in epileptogenesis located outside the temporal lobe (superior parietal gyrus, K(1), range: -3.7% to +4.5%; k(2), range: -4.2% to +5.8%). In 5 of 7 patients, ipsilateral efflux (k(2)) increases were more pronounced than ipsilateral influx (K(1)) increases, which resulted in ipsilateral reductions (10%-26%) of R-[(11)C]verapamil distribution volumes (DV). However, for none of the examined brain regions, any of the differences in K(1), k(2) and DV between the epileptogenic and the nonepileptogenic hemisphere reached statistical significance (p > 0.05, Wilcoxon matched pairs test). Conclusions: Even though we failed to detect statistically significant differences in R-[(11)C]verapamil model parameters between epileptogenic and nonepileptogenic brain regions, it cannot be excluded from our pilot data in a small sample size of patients that regionally enhanced P-gp activity might contribute to drug resistance in some patients with temporal lobe epilepsy. more...
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- 2007
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32. Preparation and radiosynthesis of [18F]FE@CFN (2-[18F]fluoroethyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate): a potential μ-opioid receptor imaging agent
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Markus Mitterhauser, Dagmar E. Ettlinger, Kurt Kletter, Leonhard-Key Mien, Wolfgang Wadsak, Rupert Lanzenberger, Robert Dudczak, Janos Marton, and Sylvia Feitscher
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Stereochemistry ,Chemistry ,medicine.drug_class ,Radiosynthesis ,Pet imaging ,Imaging agent ,Carfentanil ,chemistry.chemical_compound ,Opioid receptor ,medicine ,Organic chemistry ,Specific activity ,Physical and Theoretical Chemistry ,Fluoroethyl ,Derivative (chemistry) ,medicine.drug - Abstract
PET imaging of the μ-opioid receptor (OR) is still restricted to [11C]carfentanil ([11C]CFN) but its use is limited due to its short half-life and high agonistic potency. Recently, the radiosynthesis of [18F]fluoroalkyl esters of CFN was proposed, unfortunately yielding products not suitable for human PET due to their low specific activities. Therefore, our rationale was to develop a reliable radiosynthesis of a [18F]fluoroethylated CFN derivative overcoming these drawbacks. The [18F]fluoroethyl ester of carfentanil, [18F]FE@CFN (2-[18F]fluoroethyl 4-[N-(1-oxopropyl)-N-phenylamino]-1-(2-phenylethyl)-4-piperidinecarboxylate), and its corresponding inactive standard compound were prepared. Purification of [18F]FE@CFN was achieved via a simple solid phase extraction method. [18F]FE@CFN was prepared with excellent purity (> 98%) and sufficient yields. Specific activity surpassed the level required for safe administration. We therefore conclude that our simplified synthesis of [18F]FE@CFN, for the first time, overcomes the shortcomings of [11C]CFN and the previously suggested alternatives, namely, (1) longer half-life; (2) easy production and (3) adequate specific activity, should make a wider application possible. Hence, [18F]FE@CFN may become a valuable PET tracer for the imaging of the μ-OR in human brain and heart. more...
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- 2007
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33. Comparison of11C-acetate positron emission tomography and67Gallium citrate scintigraphy in patients with hepatocellular carcinoma
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Elke Grumbeck, Markus Peck-Radosavljevic, Mohsen Beheshti, Stylianos Kapiotis, Robert Dudczak, Simon Oezer, Monika Schmid, Kurt Kletter, Shuren Li, and Gerhard Hamilton
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Male ,medicine.medical_specialty ,Carcinoma, Hepatocellular ,Nuclear imaging ,Gallium ,Single-photon emission computed tomography ,Scintigraphy ,Left supraclavicular lymph node ,67 Gallium ,medicine ,Humans ,In patient ,Carbon Radioisotopes ,Citrates ,Prospective Studies ,Radionuclide Imaging ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Hepatology ,medicine.diagnostic_test ,business.industry ,Liver Neoplasms ,Middle Aged ,medicine.disease ,Positron emission tomography ,Positron-Emission Tomography ,Hepatocellular carcinoma ,Female ,Radiology ,Radiopharmaceuticals ,business ,Nuclear medicine - Abstract
AIMS Nuclear imaging may have an increasing role in the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to compare prospectively the Gallium-67 citrate ((67)Ga) scintigraphy results with those obtained by positron emission tomography (PET) using (11)C-acetate in patients with HCC. METHODS We prospectively analysed 21 patients (mean age, 64+/-11 years) with histopathologically verified HCC undergoing (11)C-acetate PET and (67)Ga scintigraphy. (67)Ga scans were not performed in three of these 21 patients due to the exacerbation of the disease. Whole-body (11)C-acetate PET were performed following intravenous injection of 850 MBq of (11)C-acetate. For (67)Ga scintigraphy, whole-body, planar and single photon emission computed tomography imaging acquisitions were performed after intravenous application of a mean dose of 189 MBq (67)Ga. RESULTS (67)Ga scintigraphy found abnormalities only in 10 of 18 patients (56%) and detected 22 of 46 clinically involved sites (48%); it was false-positive in two patients. (11)C-acetate PET found abnormalities in 14 of 18 patients (78%) and detected 36 of 46 clinical lesions (78%); it was false-positive in one patients. In one patient with left supraclavicular lymph node metastases, neither the (67)Ga scintigraphy nor the conventional computed tomography have shown the lesions, which were clearly demonstrated by the (11)C-acetate PET. CONCLUSION Our results indicate significantly higher sensitivity and specificity of (11)C-acetate PET than (67)Ga scan in detection of HCC lesions. This study suggests that imaging with (11)C-acetate PET might play a potential role in the diagnostic workup of patients with HCC. more...
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- 2006
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34. [18F]FETO: metabolic considerations
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Leonhard-Key Mien, Markus Mitterhauser, Georgios Karanikas, Wolfgang Wadsak, Leila Wabnegger, Robert Dudczak, Helmut Viernstein, Kurt Kletter, Michael Machek, Dagmar E. Ettlinger, and Gundula Rendl
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medicine.medical_specialty ,Metabolic Clearance Rate ,Andrology ,Carboxylesterase ,Pharmacokinetics ,In vivo ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,reproductive and urinary physiology ,chemistry.chemical_classification ,Adrenal cortex ,Imidazoles ,General Medicine ,Metabolism ,Metomidate ,female genital diseases and pregnancy complications ,In vitro ,Endocrinology ,Enzyme ,medicine.anatomical_structure ,chemistry ,embryonic structures ,Steroid 11-beta-Hydroxylase ,Radiopharmaceuticals ,medicine.drug - Abstract
11beta-Hydroxylase is a key enzyme in the biosynthesis of adrenocortical steroid hormones and is a suitable target for the imaging of the adrenal cortex. [(11)C]Metomidate (MTO), [(11)C]etomidate (ETO) and desethyl-[(18)F]fluoroethyl-etomidate (FETO) are potent inhibitors of this enzyme and are used for PET imaging of adrenocortical pathologies. The aims of this study were (1) to evaluate and compare the metabolic stability of MTO, ETO and FETO against esterases and (2) to investigate the metabolic pattern of FETO in vivo.In vitro assays were performed using different concentrations of MTO, ETO and FETO with constant concentrations of carboxylesterase. Human in vivo studies were performed with human blood samples drawn from the cubital vein. After sample clean-up, the serum was analysed by HPLC methods.In vitro assays showed Michaelis-Menten constants of 115.1 mumol for FETO, 162.0 mumol for MTO and 168.6 mumol for ETO. Limiting velocities were 1.54 mumol/min (FETO), 1.47 mumol/min (MTO) and 1.35 mumol/min (ETO). This implies insignificantly decreased esterase stability of FETO compared with MTO and ETO. In vivo investigations showed a rapid metabolisation of FETO within the first 10 min (2 min: 91.41%+/-6.44%, n=6; 10 min: 23.78%+/-5.54%, n=4) followed by a smooth decrease in FETO from 20 to 90 min (20 min: 11.23%+/-3.79% n=4; 90 min: 3.68%+/-3.65%, n=4). Recovery rate was 61.43%+/-3.19% (n=12).In vitro experiments demonstrated that FETO stability against esterases is comparable to that of ETO and MTO. The metabolic profile showed that FETO kinetics in humans are fast. more...
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- 2006
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35. [18F]FETO for adrenocortical PET imaging: a pilot study in healthy volunteers
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Kurt Kletter, Leonhard-Key Mien, Georgios Karanikas, Dagmar E. Ettlinger, Gundula Rendl, Robert Dudczak, Wolfgang Wadsak, Matthias Schuetz, and Markus Mitterhauser
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Adult ,Male ,medicine.medical_specialty ,Pathology ,Metabolic Clearance Rate ,Whole body imaging ,Pilot Projects ,Reference Values ,Internal medicine ,Healthy volunteers ,medicine ,Humans ,Tissue Distribution ,Whole Body Imaging ,Radiology, Nuclear Medicine and imaging ,Pet tracer ,medicine.diagnostic_test ,business.industry ,Adrenal cortex ,Imidazoles ,General Medicine ,Pet imaging ,Middle Aged ,Functional imaging ,Endocrinology ,medicine.anatomical_structure ,Organ Specificity ,Positron emission tomography ,Positron-Emission Tomography ,Reference values ,Adrenal Cortex ,Female ,Radiopharmaceuticals ,business - Abstract
Functional imaging of the adrenal cortex by means of PET may play an important clinical role. Recently, we presented the synthesis and first evaluation of a novel 11beta-hydroxylase inhibitor, [(18)F]FETO, in rats displaying high tracer accumulation in the adrenals. In this study, we aimed to investigate for the first time the potency of [(18)F]FETO as a PET tracer for the adrenal cortex in humans.An average preparation yielded 1-2 GBq of [(18)F]FETO ready to use. Ten healthy volunteers aged 24-57 years (five male and five female) were included in the study. After i.v. administration of 365 MBq [(18)F]FETO (246-391 MBq), dynamic images were acquired in 2D standard mode in 14 frames over 45 min. Afterwards, whole-body scanning was performed. In addition to visual interpretation, semi-quantitative analysis using standardised uptake values (SUVs) was conducted.[(18)F]FETO distribution was similar in all scanned volunteers. Visually, pronounced accumulation of [(18)F]FETO was found in the adrenals, whereas moderate uptake was observed-at least in some of the subjects-for liver, renal calices, gallbladder, stomach walls and pancreas. Kidney and bowels showed only faint uptake. Median SUVs for the right and left adrenal glands were 15.6 (10.0-28.6) and 15.7 (10.3-35.9), respectively. The reference tissue (liver) displayed a median SUV of 2.5 (2.2-4.6).[(18)F]FETO is a valuable tracer for adrenocortical PET imaging, combining the longer half-life of( 18)F with a high 11beta-hydroxylase selectivity. In accordance with our findings in rats, FETO PET revealed very high accumulation in the adrenal glands in healthy volunteers. more...
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- 2006
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36. NCA nucleophilic radiofluorination on substituted benzaldehydes for the preparation of [18F]fluorinated aromatic amino acids
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Dagmar E. Ettlinger, Leonhard-Key Mien, Markus Mitterhauser, Barbara Wirl-Sagadin, Kurt Kletter, Bernhard K. Keppler, Wolfgang Wadsak, and Robert Dudczak
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Fluorine Radioisotopes ,Radiation ,Chemistry ,Synthon ,Hydrocarbons, Aromatic ,Amino Acids, Aromatic ,chemistry.chemical_compound ,Nucleophile ,Nucleophilic aromatic substitution ,Benzaldehydes ,Isotope Labeling ,Aromatic amino acids ,Organic chemistry ,Solid phase extraction ,Radiopharmaceuticals - Abstract
Nucleophilic aromatic substitution is a challenging task in radiochemistry. Therefore, a thorough evaluation and optimisation of this step is needed to provide a satisfactory tool for the routine preparation of [(18)F]fluorinated aromatic amino acids. Two methods, already proposed elsewhere, were evaluated and improved. The yields for the radiofluorination were increased whereas activity loss during solid phase extraction was observed. Radiochemical yields for the two methods were 92.7+/-5.5% (method 1) and 92.1+/-12.3% (method 2) for conversion and 11.1+/-2.8% (method 1) and 34.8+/-0.6% (method 2) for purification, respectively. In total, we demonstrate an optimised method for the preparation of this important class of [(18)F]fluorinated synthons for PET. more...
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- 2006
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37. Uptake of bone-seekers is solely associated with mineralisation! A study with 99mTc-MDP, 153Sm-EDTMP and 18F-fluoride on osteoblasts
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Robert Dudczak, Karoline Wiesner, Wolfgang Wadsak, Dagmar E. Ettlinger, Joseph Nguemo, Oskar Hoffmann, Leonhard-Key Mien, Helmut Viernstein, Kurt Kletter, Markus Mitterhauser, and Stefan Toegel
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Fluorine Radioisotopes ,Metabolic Clearance Rate ,Cell number ,Bone imaging ,Technetium Tc 99m Medronate ,Models, Biological ,Bone and Bones ,Mice ,Calcification, Physiologic ,Organophosphorus Compounds ,Adsorption ,Organometallic Compounds ,medicine ,Animals ,Computer Simulation ,Radiology, Nuclear Medicine and imaging ,Radionuclide Imaging ,Cells, Cultured ,Osteoblasts ,Chemistry ,business.industry ,Osteoblast ,General Medicine ,medicine.disease ,153sm edtmp ,medicine.anatomical_structure ,Cell culture ,Biophysics ,Radiopharmaceuticals ,Nuclear medicine ,business ,18f fluoride ,Calcification - Abstract
Although polyphosphonates (PPs) were introduced as bone imaging agents in nuclear medicine in the early 1970s, the mechanisms involved in their uptake still remain unclear. Suggested mechanisms range from mineral adsorption with disputed binding to the organic phase, over incorporation into the mineralisation process to a combination of both mechanisms. Thus, our investigations aimed to: (1) evaluate adsorption parameters of (99m)Tc-MDP, (153)Sm-EDTMP and (18)F-fluoride on mineralising osteoblast cultures, (2) correlate the radiotracer binding measured in the cell cultures with binding values from our previously presented mineral model and (3) compare binding with cell number.Primary osteoblasts were obtained by sequential digestion of foetal mice calvariae. The cells were incubated with 0.3 mumol of radiolabelled PPs or 25 MBq (18)F-fluoride for 120 min. Gamma signals from labelled samples were detected with a Millennium Hawkeye SPECT camera or with a dedicated Advance full-ring PET scanner and the binding percentages were calculated.From days 8 to 15 of culture, the percent binding of all evaluated tracers increased significantly, whereas the protein concentration showed insignificant changes. Additional comparisons of the binding values with our recently published pre-vivo model revealed remarkable agreement, suggesting solely bone-forming minerals to be responsible for radiotracer binding.This study provides evidence that binding of the evaluated radiotracers is not associated with osteoblast numbers but only with the concentration of bone-forming minerals. The presented correlations substantiate our recently presented pre-vivo model for the evaluation of bone-seekers: mechanisms associated with the uptake of bone-seekers are irreversible and mineral-associated processes. more...
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- 2006
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38. FDG gamma camera PET equipped with one inch crystal and XCT
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Mohsen Beheshti, Georg Dobrozemsky, Robert Dudczak, Kurt Kletter, S. Oezer, Aliasghar Khorsand, Christian Pirich, and Senta Graf
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Male ,Coronary Disease ,For Attenuation Correction ,Imaging phantom ,law.invention ,Fluorodeoxyglucose F18 ,law ,medicine ,Humans ,Gamma Cameras ,Radiology, Nuclear Medicine and imaging ,Aged ,Gamma camera ,medicine.diagnostic_test ,Phantoms, Imaging ,business.industry ,Reproducibility of Results ,Equipment Design ,General Medicine ,Gold standard (test) ,Middle Aged ,Positron emission tomography ,Positron-Emission Tomography ,Female ,Tomography ,Radiopharmaceuticals ,business ,Nuclear medicine ,Correction for attenuation ,Perfusion - Abstract
SummaryMetabolic imaging with 2-[fluorine-18]-fluoro- 2-deoxy-D-glucose (FDG) is actually considered as the best method to detect and quantitatively assess myocardial tissue viability. The aim of this study was to investigate the accuracy of FDG gamma camera positron emission tomography (GCPET) imaging equipped with one inch NaI crystals in comparison to FDG dedicated PET (dPET) imaging as a „gold standard“ in phantom and clinical studies. Patients, methods: Nineteen patients with coronary artery disease (CAD) underwent both imaging modalities. Phantom and clinical GCPET imaging were performed with a dual-headed, coincidence based gamma camera equipped with 1 inch thick NaI crystals and an x-ray tube (XCT) for attenuation correction (AC), as well as with a dedicated PET scanner with AC. 99mTc tetrofosmin single-photon emission tomography (SPET) studies were performed for assessment of myocardial perfusion, with AC. Results: Phantom studies showed a significant relation in segmental activity between FDG imaging with AC using GCPET and dPET (r = 0.91, p more...
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- 2006
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39. Synthesis of fluorine-18-labelled 5- and 6-fluoro-2-pyridinamine
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Thomas Erker, Peter Angelberger, Kurt Kletter, Markus Müller, Aiman Abrahim, Christian Joukhadar, and Oliver Langer
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Chemistry ,Organic Chemistry ,Radiosynthesis ,Total synthesis ,Biochemistry ,Chemical synthesis ,Analytical Chemistry ,chemistry.chemical_compound ,Nucleophile ,Nucleophilic aromatic substitution ,Drug Discovery ,Pyridine ,Organic chemistry ,Radiology, Nuclear Medicine and imaging ,Rearrangement reaction ,Hofmann rearrangement ,Spectroscopy - Abstract
A one-pot radiosynthesis method to prepare the new fluorine-18-labelled fluoropyridine derivatives 5-[18F]fluoro-2-pyridinamine and 6-[18F]fluoro-2-pyridinamine in two to three reaction steps was developed. The first step consisted of no-carrier-added nucleophilic aromatic substitution of commercially available halogen-substituted 2-pyridinecarboxamide or 2-pyridinecarbonitrile derivatives with K[18F]F-K222 in DMSO at 150–180°C. The [18F]fluoride incorporation yields ranged from 67 to 98% for all studied precursor molecules. It is remarkable that 5-bromo-2-pyridinecarbonitrile gave almost quantitative [18F]fluoride incorporation at the meta-position (5-position) of the pyridine ring after only 5 min of heating at 150°C. After base-catalysed hydrolysis of the [18F]fluorinated pyridinecarbonitriles into their corresponding carboxamides, the latter were transformed in a Hofmann-type rearrangement reaction into the respective amines by treatment of crude reaction mixtures with bromine and aqueous base (20–30% conversion yield). Reaction mixtures were purified by reversed-phase semipreparative HPLC followed by strong cation exchange solid-phase extraction to afford 5-[18F]fluoro-2-pyridinamine and 6-[18F]fluoro-2-pyridinamine in non-decay-corrected radiochemical yields of 6–10% in a total synthesis time of 83–112 min. The preparation of 5-[18F]fluoro-2-pyridinamine is one of very few examples demonstrating the feasibility of nucleophilic meta-[18F]fluorination of a pyridine derivative. Both 5-[18F]fluoro-2-pyridinamine and 6-[18F]fluoro-2-pyridinamine are new potentially useful radiolabelled synthons for radiopharmaceutical chemistry. Copyright © 2006 John Wiley & Sons, Ltd. more...
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- 2006
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40. Colonic spread and serum pharmacokinetics of budesonide foam in patients with mildly to moderately active ulcerative colitis
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H. Brunner, C. Schrolnberger, Markus Müller, Harald Vogelsang, R. Greinwald, H. Kvaternik, Hans-Georg Eichler, Robert Dudczak, Martin Brunner, and Kurt Kletter
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Male ,Budesonide ,medicine.medical_specialty ,Colon ,medicine.drug_class ,Anti-Inflammatory Agents ,Cmax ,Proctosigmoiditis ,Proctocolitis ,Gastroenterology ,Descending colon ,Administration, Rectal ,Internal medicine ,medicine ,Humans ,Gamma Cameras ,Pharmacology (medical) ,Prospective Studies ,Radionuclide Imaging ,Hepatology ,business.industry ,Technetium ,Sigmoid colon ,medicine.disease ,Ulcerative colitis ,Surgery ,medicine.anatomical_structure ,Tolerability ,Corticosteroid ,Colitis, Ulcerative ,Female ,business ,medicine.drug - Abstract
Summary Background : Local treatment with foams in patients suffering from ulcerative proctitis or proctosigmoiditis is considered a rational treatment option. Aims : To investigate colonic spread, safety, tolerability and acceptance of a newly developed budesonide foam formulation. Methods : Twelve patients (four females, eight males) with acute proctosigmoiditis or left-sided ulcerative colitis were rectally administered a single dose of [99Tcm]-labelled budesonide foam (Budenofalk; Dr Falk Pharma GmbH, Freiburg, Germany) containing 2 mg budesonide in 20 mL foam after diagnostic colonoscopy. Thereafter, the colonic spread was assessed by means of γ-scintigraphy for 6 h. Serum samples were taken simultaneously. Results : Budesonide foam spread with a maximum between 11 and 40 cm, thus reaching the sigmoid colon in all patients. In some patients, the foam even extended into the distal third and the middle of the descending colon with maximum radioactivity at 4 h. Systemic budesonide absorption was rapid and pharmacokinetic data were comparable with published data on marketed budesonide enemas, with mean serum Cmax and AUC0-8h values of 0.8 ± 0.5 ng/mL and 3.7 ± 1.9 ng h/mL, respectively. The new formulation was well accepted by all patients, who could retain the foam for at least 4 h. Conclusions : In the majority of patients, budesonide foam effectively spread up to the left-sided colon and thus qualifies for the local treatment of proctosigmoiditis. more...
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- 2005
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41. Influence of functional haplotypes in the drug transporter gene on central nervous system drug distribution in humans
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Georg Dobrozemsky, Christoph Baumgartner, Markus Müller, Wolfgang Wadsak, Andreas Krcal, Rudolf Karch, Kurt Kletter, Ilka Steiner, Martin Brunner, Raute Sunder-Plassmann, Ulrich Müller, Oliver Langer, Christine Mannhalter, and Robert Dudczak more...
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Pharmacology ,Central nervous system ,Haplotype ,Single-nucleotide polymorphism ,Biology ,Confidence interval ,medicine.anatomical_structure ,Pharmacokinetics ,medicine ,Verapamil ,Distribution (pharmacology) ,Pharmacology (medical) ,Blood drawing ,medicine.drug - Abstract
Background and Objective Single nucleotide polymorphisms in the human multidrug-resistance gene ABCB1 have been reported to be associated with altered expression and function of P-glycoprotein, an efflux transporter, expressed at the blood-brain barrier. To test whether certain ABCB1 haplotypes contribute to interindividual differences in central nervous system drug distribution, brain distribution of a model P-glycoprotein substrate, the calcium channel inhibitor verapamil, was measured by positron emission tomography (PET) in 2 groups of healthy volunteers. Methods Ten homozygous carriers (cases) of the TTT haplotype (3435T, 1236T, and 2677T) and 10 controls homozygous for the wild-type CGC haplotype (3435C, 2677G, and 1236C) were administered a mean intravenous bolus of 412 ± 114 MBq carbon 11-labeled verapamil containing less than 15 nmol of unlabeled verapamil. PET imaging of brain tissue and venous blood sampling were performed for 1 hour after dosing. Results As a measure of brain penetration, the ratio of PET area under the time-radioactivity curve (AUC) to plasma AUC was calculated from time-radioactivity curves, with a mean ratio of 1.1 ± 0.3 (SD) (95% confidence interval, 0.9–1.3) for cases and 1.1 ± 0.2 (95% confidence interval, 0.9–1.2) for controls, respectively (P = .96). Mean brain AUC values were 31.2 ± 3.9 and 35.7 ± 5.7 for the TTT and CGC haplotype, respectively (P = .11). Plasma AUCs were not significantly different. Conclusion No difference in the brain distribution of [11C]verapamil could be detected in healthy volunteers differing in ABCB1 haplotypes. Clinical Pharmacology & Therapeutics (2005) 78, 182–190; doi: 10.1016/j.clpt.2005.04.011 more...
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- 2005
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42. FDG PET is superior to CT in the prediction of viable tumour in post-chemotherapy seminoma residuals
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Kurt Kletter, C. Dittrich, Georgios Karanikas, Monica Szabó, Bernhard M. Dohmen, Alexander Becherer, Jörg Pont, Maria De Santis, Robert Dudczak, and Carsten Bokemeyer
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Adult ,Male ,Radiography, Abdominal ,Neoplasm, Residual ,medicine.medical_treatment ,Radiography ,Sensitivity and Specificity ,Metastasis ,Lesion ,Testicular Neoplasms ,Fluorodeoxyglucose F18 ,Predictive Value of Tests ,Abdomen ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prospective Studies ,Prospective cohort study ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,General Medicine ,Seminoma ,Middle Aged ,Thorax ,medicine.disease ,Radiographic Image Enhancement ,Positron emission tomography ,Positron-Emission Tomography ,Predictive value of tests ,Radiography, Thoracic ,Radiopharmaceuticals ,medicine.symptom ,Nuclear medicine ,business ,Tomography, Spiral Computed ,Follow-Up Studies - Abstract
In advanced seminoma the management of residuals after completion of chemotherapy is controversial. Some centres routinely perform surgery for lesionsor =3 cm diameter, others recommend surgery solely if the residual fail to shrink or show even growth. This study prospectively investigates whether FDG PET can improve the prediction of viable tumour in post-chemotherapy seminoma residuals.After an expansion of a previous study population, 54 patients from eight centres with metastatic seminoma and a CT-documented mass after chemotherapy were included in the study. Six patients were excluded from evaluation because of protocol violations. After PET, the patients underwent either surgery or were followed clinically. On follow-up the lesions were considered to be non-viable when there was unequivocal shrinking, or when the lesion remained morphologically stable for at least 24 months. Any lesion growth was assumed to be malignant. PET results were compared to CT discrimination (oror =3 cm) of the residual masses.Fifty-two PET scans were evaluable. After adequate chemotherapy, there were 74 CT-documented residual masses ranging in size from 1 to 11 cm (median, 2.2 cm). Their dignities were confirmed histologically in 13 lesions, or by follow-up CT in 61 lesions. Four of forty-seven lesions3 cm and 11/27 lesionsor =3 cm were viable. PET was true positive in one lesion3 cm and in 11 lesionsor =3 cm, false negative in three lesions3 cm, and true negative in 59 lesions (43 lesions3 cm). No PET scan was false positive. In detecting viability the sensitivity and specificity was 73% (95% CI, 44-88), and 73% (59-83), respectively, for CT (oror =3 cm); and 80% (51-95), and 100% (93-100), respectively, for PET (specificity, P0.001).In post-chemotherapy seminoma residuals, a positive PET is highly predictive for the presence of viable tumour. The specificity of PET is significantly higher than that of CT when using aor =3 cm cut-off. A negative PET scan is excellent for the exclusion of disease in lesionsor =3 cm, with a somewhat higher sensitivity than CT (n.s.). PET can contribute to the management of residual seminoma lesions, especially in terms of avoiding unnecessary additional treatment for patients with lesionsor =3 cm. more...
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- 2005
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43. Synthesis of 1,1′ [11C]-methylene-di-(2-naphthol) ([11C]ST1859) for PET studies in humans
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Alexander Schmid, Diana Celona, Markus Müller, Andreas Krcal, Kurt Kletter, Aiman Abrahim, Oliver Langer, Dirk Roeda, Patrizia Minetti, and Frédéric Dollé
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Microdosing ,Organic Chemistry ,Radiosynthesis ,Radiochemistry ,Formaldehyde ,Biochemistry ,Chemical synthesis ,Analytical Chemistry ,Catalysis ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Organic chemistry ,Radiology, Nuclear Medicine and imaging ,Dehydrogenation ,Methanol ,2-Naphthol ,Spectroscopy - Abstract
1,1′-Methylene-di-(2-naphthol) (ST1859), a candidate drug for the treatment of Alzheimer's disease, was radiolabelled with carbon-11 with the aim to perform PET microdosing studies in humans. The radiosynthesis was automated in a commercial synthesis module (Nuclear Interface PET tracer synthesizer) and proceeded via reaction of [11C]formaldehyde with 2-naphthol. [11C]formaldehyde was prepared by catalytic dehydrogenation of [11C]methanol (conversion yield: 48±11% (n = 19)) employing a recently developed silver-containing ceramic catalyst. Starting from 69±3 GBq of [11C]carbon dioxide (n = 19), 4±1 GBq of [11C]ST1859 (decay-corrected to the end of bombardment), readily formulated for intravenous administration, could be obtained in an average synthesis time of 38 min. The specific radioactivity of [11C]ST1859 at the end of synthesis exceeded 32 GBq/µmol. Copyright © 2005 John Wiley & Sons, Ltd. more...
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- 2005
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44. [ 18 F]Ciprofloxacin, a New Positron Emission Tomography Tracer for Noninvasive Assessment of the Tissue Distribution and Pharmacokinetics of Ciprofloxacin in Humans
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Oliver Langer, Ulrich Müller, Georg Dobrozemsky, Robert Dudczak, Markus Mitterhauser, Kurt Kletter, Martin Brunner, Markus Müller, Wolfgang Wadsak, and Markus Zeitlinger
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Adult ,Male ,Quality Control ,Fluorine Radioisotopes ,Biodistribution ,Excretion ,Pharmacokinetics ,Ciprofloxacin ,medicine ,Humans ,Tissue Distribution ,Pharmacology (medical) ,Antibacterial agent ,Pharmacology ,medicine.diagnostic_test ,business.industry ,Brain ,Half-life ,Anti-Bacterial Agents ,Infectious Diseases ,Positron emission tomography ,Positron-Emission Tomography ,Radiopharmaceuticals ,Nuclear medicine ,business ,Half-Life ,Blood drawing ,medicine.drug - Abstract
The biodistribution and pharmacokinetics of the fluorine-18-labeled fluoroquinolone antibiotic [ 18 F]ciprofloxacin in tissue were studied noninvasively in humans by means of positron emission tomography (PET). Special attention was paid to characterizing the distribution of [ 18 F]ciprofloxacin to select target tissues. Healthy volunteers ( n = 12) were orally pretreated for 5 days with therapeutic doses of unlabeled ciprofloxacin. On day 6, subjects received a tracer dose (mean injected amount, 700 ± 55 MBq, which contained about 0.6 mg of unlabeled ciprofloxacin) of [ 18 F]ciprofloxacin as an intravenous bolus. Thereafter, PET imaging and venous blood sampling were initiated. Time-radioactivity curves were measured for liver, kidney, lung, heart, spleen, skeletal muscle, and brain tissues for up to 6 h after radiotracer administration. The first application of [ 18 F]ciprofloxacin in humans has demonstrated the safety and utility of the newly developed radiotracer for pharmacokinetic PET imaging of the tissue ciprofloxacin distribution. Two different tissue compartments of radiotracer distribution could be identified. The first compartment including the kidney, heart, and spleen, from which the radiotracer was washed out relatively quickly (half-lives [ t 1/2 s], 68, 57, and 106 min, respectively). The second compartment comprised liver, muscle, and lung tissue, which displayed prolonged radiotracer retention ( t 1/2 , >130 min). The highest concentrations of radioactivity were measured in the liver and kidney, the main organs of excretion (standardized uptake values [SUVs], 4.9 ± 1.0 and 9.9 ± 4.4, respectively). The brain radioactivity concentrations were very low (−1 ) and could therefore not be quantified. Transformation of SUVs into absolute concentrations (in micrograms per milliliter) allowed us to relate the concentrations at the target site to the susceptibilities of bacterial pathogens. In this way, the frequent use of ciprofloxacin for the treatment of a variety of infections could be corroborated. more...
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- 2004
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45. In vitro and in vivo evaluation of [18F]ciprofloxacin for the imaging of bacterial infections with PET
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Wolfgang Wadsak, Oliver Langer, Markus Zeitlinger, Sophie Ziegler, Ulrich Müller, Robert Dudczak, Georg Dobrozemsky, Erich Minar, Kurt Kletter, Christian Joukhadar, Markus Mitterhauser, Edith Lackner, Markus Müller, and Martin Brunner more...
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Male ,Fluorine Radioisotopes ,Pathology ,medicine.medical_specialty ,Metabolic Clearance Rate ,Vascular permeability ,Sensitivity and Specificity ,Microbiology ,Fluoroquinolone Antibiotic ,Ciprofloxacin ,In vivo ,Escherichia coli ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Aged ,Gamma counter ,chemistry.chemical_classification ,Reproducibility of Results ,Soft tissue ,Bacterial Infections ,General Medicine ,In vitro ,Enzyme ,chemistry ,Positron-Emission Tomography ,Female ,Radiopharmaceuticals ,medicine.drug - Abstract
The suitability of the 18F-labelled fluoroquinolone antibiotic ciprofloxacin ([18F]ciprofloxacin) for imaging of bacterial infections with positron emission tomography (PET) was assessed in vitro and in vivo.For the in vitro experiments, suspensions of various E. coli strains were incubated with different concentrations of [18F]ciprofloxacin (0.01-5.0 microg/ml) and radioactivity retention was measured in a gamma counter. For the in vivo experiments, 725 +/- 9 MBq [18F]ciprofloxacin was injected intravenously into four patients with microbiologically proven bacterial soft tissue infections of the lower extremities and time-radioactivity curves were recorded in infected and uninfected tissue for 5 h after tracer injection.Binding of [18F]ciprofloxacin to bacterial cells was rapid, non-saturable and readily reversible. Moreover, bacterial binding of the agent was similar in ciprofloxacin-resistant and ciprofloxacin-susceptible clinical isolates. These findings suggest that non-specific binding rather than specific binding to bacterial type II topoisomerase enzymes is the predominant mechanism of bacterial retention of the radiotracer. PET studies in the four patients with microbiologically proven bacterial soft tissue infections demonstrated locally increased radioactivity uptake in infected tissue, with peak ratios between infected and uninfected tissue ranging from 1.8 to 5.5. Radioactivity was not retained in infected tissue and appeared to wash out with a similar elimination half-life as in uninfected tissue, suggesting that the kinetics of [18F]ciprofloxacin in infected tissue are governed by increased blood flow and vascular permeability due to local infection rather than by a binding process.Taken together, our results indicate that [18F]ciprofloxacin is not suited as a bacteria-specific infection imaging agent for PET. more...
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- 2004
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46. Radiosynthesis and in vitro evaluation of the 5HT2 receptor ligand [N-11C-methyl]-1-[2,5-dimethoxy-4-iodophenyl]-2-methylaminopropane for PET
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A. Becherer, Kurt Kletter, J. Schmaljohann, and D. GüNDISCH
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Agonist ,Chemistry ,medicine.drug_class ,Stereochemistry ,5-HT2 receptor ,Radiosynthesis ,medicine ,Physical and Theoretical Chemistry ,Serotonergic ,Ligand (biochemistry) ,Receptor ,5-HT receptor ,In vitro - Abstract
In vivo labelling of serotonergic receptors (5HT) could be a useful tool for understanding the physiological and pathophysiological role of neurodegenerative disorders. 1-[2,5-Dimethoxy-4-iodophenyl]-2-aminopropane (DOI), a well known agonist with high affinity to 5HT2 receptors, was labelled with C-11 for PET. Here we report the evaluation of the mono-methylated and dimethylated analogs of DOI for PET. The syntheses of [N-11C-methyl]-DOI ([11C]MDOI) and [N-11C-dimethyl]-DOI ([11C]DMDOI) were optimized resulting in radiochemical yields of up to 43%, allowing efficient production for clinical use. High affinities for the 5HT2A and 5HT2C receptors with a slight preference for 5HT2A were found for MDOI, similar to the highly potent hallucinogen DOI. more...
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- 2004
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47. Biological evaluation of 2′-[18F]fluoroflumazenil ([18F]FFMZ), a potential GABA receptor ligand for PET
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Werner Sieghart, Stefan Tögel, Leonhard-Key Mien, Robert Dudczak, Wolfgang Wadsak, Helmut Viernstein, Kurt Kletter, Leila Wabnegger, Oliver Langer, and Markus Mitterhauser
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Flumazenil ,Male ,Fluorine Radioisotopes ,Cancer Research ,medicine.medical_specialty ,Cerebellum ,Metabolic Clearance Rate ,medicine.drug_class ,Drug Evaluation, Preclinical ,Pharmacology ,Ligands ,Rats, Sprague-Dawley ,Receptors, GABA ,GABA receptor ,Internal medicine ,medicine ,Animals ,Tissue Distribution ,Radiology, Nuclear Medicine and imaging ,Receptor ,Benzodiazepine ,Chemistry ,Ligand ,Antagonist ,Brain ,Receptors, GABA-A ,Rats ,Cortex (botany) ,Endocrinology ,medicine.anatomical_structure ,nervous system ,Organ Specificity ,Positron-Emission Tomography ,Molecular Medicine ,Radiopharmaceuticals ,medicine.drug - Abstract
[(11)C]Flumazenil, a highly selective benzodiazepine antagonist is the most extensively used GABA(A) ligand for PET so far. To overcome half life disadvantages of (11)C a [(18)F]-labeled flumazenil derivative, 2'-[(18)F]fluoroflumazenil (FFMZ) was developed and biologically evaluated with respect to the GABA(A) receptor. Organ with the highest uptake was the pituitary gland. Brain uptake was high and followed the order cortex>thalamus>cerebellum>rest brain. Fluoroflumazenil displaced [(3)H]flumazenil binding from membrane GABA(A) receptors with an IC(50)value (3.5 nM) comparable to that of Flumazenil (2.8 nM). The presented data confirm the potential of [(18)F]FFMZ for PET imaging of the GABA-ergic system. more...
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- 2004
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48. Synthesis and biodistribution of [18F]FE@CIT, a new potential tracer for the dopamine transporter
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Leonhard-Key Mien, Robert Dudczak, Markus Mitterhauser, Wolfgang Wadsak, Alexander Hoepping, Helmut Viernstein, and Kurt Kletter
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Male ,Fluorine Radioisotopes ,Biodistribution ,Time Factors ,Nortropanes ,Nerve Tissue Proteins ,Striatum ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Animals ,Tissue Distribution ,Chromatography, High Pressure Liquid ,Serotonin transporter ,Fluoroethyl ,Dopamine transporter ,Dopamine Plasma Membrane Transport Proteins ,Membrane Glycoproteins ,Radiochemistry ,Dose-Response Relationship, Drug ,biology ,Chemistry ,Radiosynthesis ,Temperature ,Brain ,Membrane Transport Proteins ,Tropane ,Rats ,Biochemistry ,biology.protein ,Autoradiography ,Chromatography, Thin Layer ,Ex vivo - Abstract
In the last decade radiolabeled tropane analogs based on β-CIT have proven indispensable for the imaging of the dopamine transporter. However, further improvements in their pharmacodynamic and pharmacokinetic features are desirable. An important improvement, yielding in higher affinity to the dopamine transporter (DAT) vs. serotonin transporter (SERT), can be achieved by a simple replacement of the carboxylic methyl ester group in β-CIT by a fluoroethyl ester. The preparation and ex vivo evaluation of this new β-CIT-analog ([18F]FE@CIT) is presented here. Precursor and standard were prepared from β-CIT and analyzed by spectroscopic methods. Yields of precursor and standard preparation were 61% and 42%, respectively. [18F]FE@CIT was prepared by distillation of [18F]bromofluoroethane ([18F]BFE) and reaction with (1R-2-exo-3-exo)8-methyl-3-(4-iodo-phenyl)-8-azabicyclo[3.2.1] octane-2-carboxylic acid. After 10 min at 150°C the product was purified using a C-18 SepPak. The radiosynthesis evinced radiochemical yields of >90% (based on [18F]BFE), the specific radioactivity was >416 GBq/μmol. An average 30 μAh cyclotron irradiation yielded more than 2.5 GBq [18F]FE@CIT. For the ex vivo bioevaluation, 20 male Sprague-Dawley rats were sacrificed at 5, 15, 30, 60, and 120 min after injection. Organs were removed, weighed, and counted. For autoradiographic experiments, transverse brain slices of about 100 μm were prepared. The ex vivo evaluation showed highest brain uptake in striatal regions, followed by thalamus and cerebellum. The highest striatum to cerebellum ratio was 3.73 and the highest thalamus to cerebellum ratio was 1.65. Autoradiographic images showed a good and differentiated uptake in striatal regions with a good target-to-background ratio. Synapse 55:73–79, 2005. © 2004 Wiley-Liss, Inc. more...
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- 2004
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49. Radiosynthesis of 3-(2′-[18F]fluoro)-flumazenil ([18F]FFMZ)
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Leonhard-Key Mien, Kurt Kletter, Wolfgang Wadsak, Robert Dudczak, Bernhard K. Keppler, Stefan Tögel, and Markus Mitterhauser
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Flumazenilo ,Chemistry ,Stereochemistry ,Organic Chemistry ,Radiosynthesis ,Biochemistry ,Medicinal chemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Flumazenil ,Drug Discovery ,medicine ,Radiology, Nuclear Medicine and imaging ,Acetonitrile ,Trifluoromethanesulfonate ,Spectroscopy ,Fluoroethyl ,medicine.drug - Abstract
Recently, two fluorine-18 labelled derivatives of flumazenil were described: 5-(2′-[18F]fluoroethyl)-5-desmethylflumazenil (ethyl 8-fluoro-5-[18F]fluoroethyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a] [1,4]diazepine-3-carboxylate; [18F]FEFMZ) and 3-(2′-[18F]fluoro)-flumazenil (2′-[18F]fluoroethyl 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a]-[1,4]diazepine-3-carbo- xylate; [18F]FFMZ). Since the biodistribution data of the latter were superior to those of the former we developed a synthetic approach for [18F]FFMZ starting from a commercially available precursor, thereby obviating the need to prepare a precursor by ourselves. The following two-step procedure was developed: First, [18F]fluoride was reacted with 2-bromoethyl triflate using the kryptofix/acetonitrile method to yield 2-bromo-[18F]fluoroethane ([18F]BFE). In the second step, distilled [18F]BFE was reacted with the tetrabutylammonium salt of 3-desethylflumazenil (8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-benzo-[f]imidazo[1,5-a] [1,4]diazepine-3-carboxylic acid) to yield [18F]FFMZ. The synthesis of [18F]FFMZ allows for the production of up to 7 GBq of this PET-tracer, enough to serve several patients. [18F]FFMZ synthesis was completed in less than 80 min and the radiochemical purity exceeded 98%. Copyright © 2003 John Wiley & Sons, Ltd. more...
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- 2003
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50. Comparison of three different purification methods for the routine preparation of [11C] Metomidate
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Georg Zettinig, Markus Mitterhauser, Helmut Viernstein, Kurt Kletter, Joern Schmaljohann, Oliver Langer, Robert Dudczak, and Wolfgang Wadsak
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Quality Control ,Radiation ,Preparative hplc ,Chromatography ,Chemistry ,Free acid ,Adrenal Gland Neoplasms ,Solvent ,Adrenal masses ,Isotope Labeling ,11C-metomidate ,Organic chemistry ,Etomidate ,Carbon Radioisotopes ,Purification methods ,Chromatography, High Pressure Liquid ,Tomography, Emission-Computed - Abstract
PET with (R)-[O-methyl-11C] metomidate ([11C] MTO) is an attractive method for the characterisation of adrenal masses discriminating lesions of adrenal cortical origin from noncortical lesions. [11C] MTO was prepared by the reaction of [11C] methyliodide with the corresponding free acid. Three purification methods have been compared. The method of choice uses preparative HPLC with a ready-to-use weak acidic solvent. more...
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- 2003
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